Table of Contents

Essential messages ........................................................................................................................................ 1

Authors and legal information .................................................................................................................. 1
Key messages ............................................................................................................................................ 2
Gaps in evidence ....................................................................................................................................... 5
Authors and publication ............................................................................................................................... 7
Preamble ....................................................................................................................................................... 8
Introduction .................................................................................................................................................. 9
Stepwise approach to the management of patients with suspected CCS .................................................. 11
Overview ................................................................................................................................................. 11
STEP 1: General clinical examination ...................................................................................................... 12
History, differential diagnosis, and physical examination .................................................................. 12
Basic testing: 12-lead electrocardiogram and biochemistry .............................................................. 14
STEP 2: Further evaluation ...................................................................................................................... 16
Pre-test clinical likelihood of obstructive atherosclerotic coronary artery disease ........................... 16
Transthoracic echocardiography at rest ............................................................................................. 20
Exercise ECG testing ............................................................................................................................ 21
Chest X-ray .......................................................................................................................................... 22
Ambulatory ECG monitoring ............................................................................................................... 22
STEP 3: Confirming the diagnosis ............................................................................................................ 23
Anatomical imaging: Coronary computed tomography angiography (CCTA) .................................... 23
Functional imaging .............................................................................................................................. 24
Invasive tests ....................................................................................................................................... 26
Diagnostic algorithm and selection of appropriate tests.................................................................... 28
Adverse event risk assessment ........................................................................................................... 36
STEP 4: Initial therapy ............................................................................................................................. 37
Guideline-directed therapy ......................................................................................................................... 38
Patient education, lifestyle optimization for risk factor control, and exercise therapy ......................... 38
Antianginal/anti-ischaemic medication .................................................................................................. 41
General strategy.................................................................................................................................. 41
Beta-blockers ...................................................................................................................................... 41
Combination therapy .......................................................................................................................... 41
Medical therapy for event prevention .................................................................................................... 45
 Antithrombotic drugs .......................................................................................................................... 45
Lipid-lowering drugs............................................................................................................................ 51
Sodium–glucose cotransporter 2 inhibitors and glucagon-like peptide-1 receptor agonists ............ 52
Anti-inflammatory agents for event prevention................................................................................. 53
Revascularization for chronic coronary syndromes ................................................................................ 54
Overview ............................................................................................................................................. 54
Revascularization indications and modalities ..................................................................................... 54
Patient–physician shared decision-making to perform and select revascularization modality ......... 54
Institutional protocols, clinical pathways, and quality of care ........................................................... 54
Optimal assessment and treatment of specific groups .............................................................................. 61
Heart failure ............................................................................................................................................ 61
Angina/ischaemia with non-obstructive coronary arteries (ANOCA/INOCA)......................................... 62
Definition ............................................................................................................................................ 62
Diagnosis ............................................................................................................................................. 64
Management of angina/ischaemia with non-obstructive coronary arteries (ANOCA/INOCA) .......... 67
Other specific patient groups ................................................................................................................. 70
Screening for coronary artery disease in asymptomatic individuals ...................................................... 72
Long-term follow-up and adherence .......................................................................................................... 73
Overview ................................................................................................................................................. 73
Adherence and persistence .................................................................................................................... 74
Adherence to healthy lifestyle behaviours ......................................................................................... 74
Adherence to medical therapy ........................................................................................................... 75
Diagnosis of disease progression ............................................................................................................ 76
Treatment of myocardial revascularization failure................................................................................. 78
Recurrent or refractory angina/ischaemia ............................................................................................. 79
Essential messages

Authors and legal information

2024 ESC Guidelines for the management of chronic coronary syndromes*
Developed by the task force for the management of chronic coronary syndromes of the
European Society of Cardiology (ESC).
Endorsed by the European Association for Cardio-Thoracic Surgery (EACTS).
Chairpersons
Christiaan Vrints
Department of Cardiology, Antwerp
University Hospital, Edegem, Belgium
and Research Group Cardiovascular Diseases,
GENCOR, University of Antwerp, Antwerp,
Belgium
Felicita Andreotti
Cardiovascular Science Department,
Fondazione Policlinico Universitario Gemelli
IRCCS, Rome, Italy and Cardio-Thoracic
Department, Catholic University Medical
School, Rome, Italy
Task Force Members:
Konstantinos C. Koskinas (Task Force Co-ordinator) (Switzerland), Xavier Rossello (Task Force
Co-ordinator) (Spain), Marianna Adamo (Italy), James Ainslie (United Kingdom), Adrian Paul
Banning (United Kingdom), Andrzej Budaj (Poland), Ronny R. Buechel (Switzerland), Giovanni
Alfonso Chiariello (Italy), Alaide Chieffo (Italy), Ruxandra Maria Christodorescu (Romania),
Christi Deaton (United Kingdom), Torsten Doenst1 (Germany), Hywel W. Jones (United
Kingdom), Vijay Kunadian (United Kingdom), Julinda Mehilli (Germany), Milan
Milojevic1 (Serbia), Jan J. Piek (Netherlands), Francesca Pugliese (United Kingdom), Andrea
Rubboli (Italy), Anne Grete Semb (Norway), Roxy Senior (United Kingdom), Jurrien M. ten Berg
(Netherlands), Eric Van Belle (France), Emeline M. Van Craenenbroeck (Belgium), Rafael Vidal-
Perez) (Spain), Simon Winther (Denmark).
1
Representing the European Association for Cardio-Thoracic Surgery (EACTS)
ESC subspecialty communities having participated in the development of this document:
Associations: Association of Cardiovascular Nursing & Allied Professions (ACNAP), Association
for Acute CardioVascular Care (ACVC), European Association of Cardiovascular Imaging
(EACVI), European Association of Preventive Cardiology (EAPC), European Association of
Percutaneous Cardiovascular Interventions (EAPCI), Heart Failure Association (HFA).
Councils: Council for Cardiology Practice.
Working Groups: Cardiovascular Pharmacotherapy, Cardiovascular Surgery, Coronary
Pathophysiology and Microcirculation, Thrombosis.
Patient forum
*Adapted from the 2024 ESC Guidelines on the management of chronic coronary syndromes
(European Heart Journal; 2024 – doi:10.1093/eurheartj/ehae177) based on uncorrected proofs.

1
Key messages
1. Symptoms of myocardial ischaemia due to obstructive
atherosclerotic CAD overlap with those of CMD or vasospasm.
2. Similar guideline-directed cardiovascular preventive therapy is
recommended in women and men in spite of the sex differences in
the clinical presentation.
3. Inclusion of risk factors to classic pre-test likelihood models of
obstructive atherosclerotic CAD improves the identification of
patients with very low (≤5%) pre-test likelihood of
obstructive CAD in whom deferral of diagnostic testing should be
considered.
4. CACS is a reliable ‘simple’ test to modify the pre-test likelihood of
atherosclerotic obstructive CAD.
5. First-line diagnostic testing of suspected CCS should be done by
non-invasive anatomic or functional imaging.
6. Selection of the initial non-invasive diagnostic test should be based
on the pre-test likelihood of obstructive CAD, other patient
characteristics that influence the performance of non-invasive
tests, and local expertise and availability.
7. CCTA is preferred to rule out obstructive CAD and detect non-
obstructive CAD.
8. Functional imaging is preferred to correlate symptoms to
myocardial ischaemia, estimate myocardial viability, and guide
decisions on coronary revascularization.
9. PET is preferred for absolute MBF measurements,
but CMR perfusion studies may offer an alternative.
10. Selective second-line cardiac imaging with functional testing in
patients with abnormal CCTA and CCTA after abnormal functional
testing may improve patient selection for ICA.
11. ICA is recommended to diagnose obstructive CAD in individuals
with a high pre- or post-test likelihood of disease, severe symptoms
refractory to GDMT, angina at a low level of exercise, and/or high
event risk.

2
12. When ICA is indicated, it is recommended to evaluate the
functional severity of ‘intermediate’ stenoses by invasive functional
testing (FFR, iFR) before revascularization.
13. Computed FFR based on the 3-dimensional reconstruction
of ICA is emerging as a valuable alternative to wire-based coronary
pressure to evaluate the functional severity of ‘intermediate’
stenoses.
14. The use of imaging guidance is now recommended when
performing complex PCI.
15. A single antiplatelet agent, aspirin or clopidogrel, is generally
recommended long term in CCS patients with obstructive
atherosclerotic CAD.
16. For high thrombotic risk CCS patients, long-term therapy with
two antithrombotic agents is reasonable, as long as bleeding risk is
not high.
17. For CCS patients with sinus rhythm, DAPT is recommended at
the time of PCI and for 1 to 6 month(s), according to high or low
bleeding risk, respectively.
18. For CCS patients requiring OAC and
undergoing PCI, OAC and DAPT (aspirin and clopidogrel) for 1 to 4
weeks, followed by OAC and clopidogrel for up to 6 months in
patients not at high ischaemic risk and up to 12 months in patients
at high ischaemic risk, followed by OAC alone should be
considered.
19. In CCS patients with functionally significant multivessel CAD,
current evidence indicates benefit of myocardial revascularization
over GDMT alone for symptom improvement, prevention of
spontaneous MI, and reduction of cardiovascular mortality at long
follow-up.
20. Among CCS patients with normal LV function and no significant
left main or proximal LAD lesions, current evidence indicates that
myocardial revascularization over GDMT alone does not prolong
overall survival.
21. Among CCS patients with reduced LV function and ischaemic
cardiomyopathy, current evidence indicates that surgical

3
 revascularization compared with GDMT alone prolongs overall
survival at very long follow-up.
22. Among patients with complex multivessel CAD without LMCAD,
particularly in the presence of diabetes, who are clinically and
anatomically suitable for both revascularization modalities, current
evidence indicates longer overall survival after CABG than PCI.
23. Among patients who are clinically and anatomically suitable for
both revascularization modalities, a greater need for repeat
revascularization after PCI than surgery, independently of
multivessel CAD anatomical severity, has been consistently
reported with current surgical and stent technology.
24. Lifestyle and risk factor modification combined with disease-
modifying and antianginal medications are cornerstones in the
management of CCS.
25. Shared decision-making between patients and healthcare
professionals, based on patient-centred care, is paramount in
defining the appropriate therapeutic pathway for CCS patients.
Patient education is key to improve risk factor control in the long
term.
26. The relatively high prevalence of ANOCA/INOCA and its
associated MACE rate warrants improvement in the diagnosis and
treatment of affected patients.
27. Persistently symptomatic patients with suspected ANOCA/
INOCA who do not respond to GDMT should undergo invasive
coronary functional testing to determine underlying endotypes.
28. Characterization of endotypes is important to guide appropriate
medical therapy for ANOCA/INOCA patients.
29. Research on effective methods to support specific healthy
lifestyle behaviours, and sustain medication and healthy lifestyle
adherence over time, is needed.
30. More research is needed on improving the implementation of
health-promoting policies and practices in the workplace setting.

4
 Gaps in evidence
1. It remains unclear if screening for subclinical obstructive CAD in the general
population is useful. Further large-scale studies are needed to investigate the
prognostic benefit of screening and treating asymptomatic CCS in the general
population, preferably involving different geographical regions. Optimal screening
options remain to be determined for specific groups at high risk (e.g. asymptomatic
individuals with diagnosed diabetes for longer than 10 years).
2. Most studies assessing diagnostic strategies in individuals with symptoms
suspected of CCS were performed in populations with a moderate (>15%–50%) pre-
test clinical likelihood of obstructive CAD. Further studies are needed to determine
the optimal and most cost-effective diagnostic strategy in individuals with a low
(>5%–15%) pre-test clinical likelihood of obstructive CAD.
3. The current diagnosis of ANOCA/INOCA and its different endotypes is mainly
determined by invasive coronary functional testing. Further research is needed to
refine and assess non-invasive diagnostic imaging modalities for CMD. Currently
available and new non-invasive imaging modalities should be calibrated against
invasive testing allowing the use of their measurements interchangeably.
4. The role of antithrombotic therapy in CCS patients with ANOCA/INOCA remains to
be established.
5. Because of how evidence has been accrued over time, there is no clear evidence
about the existence of first- and second-line antianginal therapy. It is unclear
whether long-acting nitrates, ranolazine, nicorandil, ivabradine, trimetazidine, or any
of their combinations improve anginal symptoms more than beta-blockers or CCBs.
6. The optimal type and duration of DAPT is still uncertain in some subsets of patients
(e.g. patients with prior revascularization who might benefit from shorter or
longer DAPT strategies).
7. The long-term benefit of beta-blocker therapy in post-MI patients without reduced EF
remains to be elucidated.
8. In view of the reported positive impact of low-dose colchicine in patients with CCS in
reducing MI, stroke, and revascularization, future studies should identify whether
certain patient subgroups (e.g. those with elevated biomarker levels) might derive
even greater clinical benefit from this treatment.
9. A post-hoc analysis of ISCHEMIA detected a graded association between the
severity of obstructive CAD assessed by CCTA and all-cause mortality and
acute MI during follow-up. There is a need of randomized data comparing
contemporary medical treatment against early revascularization plus medical
therapy in subsets of patients with an increased risk for death or MI as determined
by the post-hoc analysis. Moreover, because the benefit of an invasive strategy with
respect to cardiac mortality was shown in a meta-analysis of chronologically
heterogeneous trials, including several conducted more than two decades ago, the
impact of early revascularization plus GDMT vs. contemporary GDMT on all-cause

5
 and cardiac mortality in patients with CCS should ideally be tested in a well-
designed, adequately powered randomized trial.
10. Some meta-analyses have reported a reduction in cardiac mortality without a
reduction in all-cause mortality. There is a need to clarify the impact of
revascularization in CCS patients on cardiovascular and non-cardiovascular
mortality.
11. Complete revascularization of multivessel CAD by PCI can be achieved as a single
procedure (index PCI) or as staged PCI. In the setting of CCS, the value of
staged PCI and the optimal interval between interventions needs to be evaluated.
12. Whether CABG surgery and PCI are comparable among patients with ischaemic
cardiomyopathy and HFrEF in the modern era of HF treatment needs to be
evaluated.
13. Various imaging techniques, such as low-dose DSE, CMR, and PET/CT, can identify
hibernating myocardium with the potential for functional recovery after
revascularization. Further randomized trials with contemporary, well-defined
modalities and strict adherence to protocol are needed to clarify the clinical benefits
(if any) of viability testing.
14. Residual ischaemia post-PCI, as determined by FFR/iFR, reflects remaining
atherosclerotic lesions and/or suboptimal PCI results, but also persistent or
worsening microvascular dysfunction. Whether post-PCI FFR/iFR is a ‘modifiable’
risk factor remains to be proved.
15. Among patients suitable for off-pump CABG with complex multivessel CAD but no
LMCAD, the impact of hybrid revascularization on outcomes, including peri-operative
complications other than MACE, needs more extensive investigation. Data on the
optimal time interval between MIDCAB-LIMA and PCI are lacking.
16. Whether the decision process based on a multidisciplinary Heart Team leads to
better outcomes than standard institutional practice remains to be investigated.
17. The medical therapy of ANOCA/INOCA is largely empirical. Therefore, prospective
randomized clinical trials are needed to determine the efficacy of antianginal
treatments in improving symptoms and outcomes for the different endotypes.
18. Research on effective methods to support healthy lifestyle behaviours, and sustain
medication and healthy lifestyle adherence over time, is needed. In addition, more
research is needed on improving the implementation of health-promoting policies
and practices in the workplace setting.
19. There is a need for further evidence on the effectiveness of neuromodulation, spinal
cord stimulation, therapeutic angiogenesis, and coronary sinus occlusion in patients
who suffer from refractory angina, despite guideline-directed medical treatment and
revascularization.

6
Authors and publication
2024 ESC Guidelines for the management of chronic coronary syndromes*
Developed by the task force for the management of chronic coronary syndromes of the
European Society of Cardiology (ESC).
Endorsed by the European Association for Cardio-Thoracic Surgery (EACTS).
Chairpersons
Christiaan Vrints
Department of Cardiology, Antwerp
University Hospital, Edegem, Belgium
and Research Group Cardiovascular Diseases,
GENCOR, University of Antwerp, Antwerp,
Belgium
Felicita Andreotti
Cardiovascular Science Department,
Fondazione Policlinico Universitario Gemelli
IRCCS, Rome, Italy and Cardio-Thoracic
Department, Catholic University Medical
School, Rome, Italy
Task Force Members:
Konstantinos C. Koskinas (Task Force Co-ordinator) (Switzerland), Xavier Rossello (Task Force
Co-ordinator) (Spain), Marianna Adamo (Italy), James Ainslie (United Kingdom), Adrian Paul
Banning (United Kingdom), Andrzej Budaj (Poland), Ronny R. Buechel (Switzerland), Giovanni
Alfonso Chiariello (Italy), Alaide Chieffo (Italy), Ruxandra Maria Christodorescu (Romania),
Christi Deaton (United Kingdom), Torsten Doenst1 (Germany), Hywel W. Jones (United
Kingdom), Vijay Kunadian (United Kingdom), Julinda Mehilli (Germany), Milan
Milojevic1 (Serbia), Jan J. Piek (Netherlands), Francesca Pugliese (United Kingdom), Andrea
Rubboli (Italy), Anne Grete Semb (Norway), Roxy Senior (United Kingdom), Jurrien M. ten Berg
(Netherlands), Eric Van Belle (France), Emeline M. Van Craenenbroeck (Belgium), Rafael Vidal-
Perez) (Spain), Simon Winther (Denmark).
1
Representing the European Association for Cardio-Thoracic Surgery (EACTS)
ESC subspecialty communities having participated in the development of this document:
Associations: Association of Cardiovascular Nursing & Allied Professions (ACNAP), Association
for Acute CardioVascular Care (ACVC), European Association of Cardiovascular Imaging
(EACVI), European Association of Preventive Cardiology (EAPC), European Association of
Percutaneous Cardiovascular Interventions (EAPCI), Heart Failure Association (HFA).
Councils: Council for Cardiology Practice.
Working Groups: Cardiovascular Pharmacotherapy, Cardiovascular Surgery, Coronary
Pathophysiology and Microcirculation, Thrombosis.
Patient forum
*Adapted from the 2024 ESC Guidelines on the management of chronic coronary syndromes
(European Heart Journal; 2024 – doi:10.1093/eurheartj/ehae177) based on uncorrected proofs.

7
Preamble

ESC Classes of recommendations and levels of evidence

Table 1 Classes of recommendations

Definition Wording to use

Class Evidence and/or general agreement that a Is recommended

I given treatment or procedure is beneficial, or is indicated
useful, effective.

Class Conflicting evidence and/or a divergence of opinion about the

II usefulness/efficacy of the given treatment or procedure.

Class Weight of evidence/opinion is in favour of Should be

IIa usefulness/efficacy. considered

Class Usefulness/efficacy is less well established May be considered

IIb by evidence/opinion.

Class Evidence or general agreement that the given Is not

III treatment or procedure is not useful/ effective, recommended
and in some cases may be harmful.

Table 2 Levels of evidence

Level of Data derived from multiple randomized clinical trials or

evidence A meta-analyses.

Level of Data derived from a single randomized clinical trial or

evidence B large non-randomized studies.

Level of Consensus of opinion of the experts and/or small studies,

evidence C retrospective studies, registries.

8
Introduction

The European Society of Cardiology (ESC) has recently completed a

comprehensive review of the existing state of medical evidence and clinical
trial data relating to the management of chronic coronary syndromes.
Classes of recommendations and levels of evidence have been evaluated
and scored according to the definitions shown in Table 1 and Table 2.
This quick reference booklet summarizes clinical care information
extracted from the full guidelines. For greater details, please refer to the
published full guideline available at www.escardio.org/guidelines.
Our understanding of the pathophysiology of CCS is transitioning from a
simple to a more complex and dynamic model. Current concepts have
broadened to embrace structural and functional abnormalities in both the
macro- and microvascular compartments of the coronary tree that may
lead to transient myocardial ischaemia.
Therefore, a new, more comprehensive definition of chronic coronary
syndromes (CCS) is introduced (Figure 1):
“CCS are a range of clinical presentations (syndromes) that arise due to
structural and/or functional alterations related to chronic diseases of the
coronary arteries and/or microcirculation. These alterations can lead to
transient, reversible, myocardial demand versus blood supply mismatch
resulting in hypoperfusion (ischaemia), usually (but not always) provoked
by exertion, emotion or other stress, and may manifest as angina, other
chest discomfort, dyspnoea, or be asymptomatic. Although stable for long
periods, chronic coronary diseases are frequently progressive and may
destabilise at any moment with the development of an acute coronary
syndrome (ACS).”
Figure 1 legend
ACS, acute coronary syndrome; ANOCA, angina with non-obstructive
coronary arteries; CABG, Coronary artery bypass grafting; CAD, coronary
artery disease; CCS, chronic coronary syndrome; INOCA, ischaemia with
nonobstructive coronary arteries; LV, left ventricular; LVEDP, left ventricular
end-diastolic pressure; PCI, percutaneous coronary intervention; VSMC,
vascular smooth muscle cell.

9
Figure 1 Central illustration: Clinical presentations of CCS and
mechanisms of myocardial ischaemia

10
Stepwise approach to the management of patients with
suspected CCS

Overview

Managing patients with suspected CCS involves four steps (Figure 2).
Figure 2 Stepwise approach to the management of patients with
suspected CCS

11
ANOCA, angina with nonobstructive coronary arteries; CAD, coronary artery
disease; CCS, chronic coronary syndrome; CCTA, coronary computed
tomography angiography; ECG, electrocardiogram; ED, emergency
department; GDMT, guideline-directed medical therapy; INOCA, ischaemia
with non-obstructive coronary arteries.
a
In selected patients. b Consider also coronary spasm or microvascular
dysfunction

STEP 1: General clinical examination

History, differential diagnosis, and physical examination

Careful history-taking is the initial diagnostic step for all clinical

scenarios within the spectrum of CCS. Although chest pain or
discomfort (Figure 3) is a cardinal symptom (angina), many
patients do not present with characteristic symptoms and the
description may vary with age, sex, race, socioeconomic class,
and geographical location.

12
Figure 3 Main CCS symptoms: angina and exertional dyspnoea

CCS, chronic coronary syndrome

13
 Basic testing: 12-lead electrocardiogram and
biochemistry

Basic testing in individuals with suspected CCS includes a 12-lead

electrocardiogram, standard laboratory tests, resting echocardiography,
and, in selected patients, a chest X-ray, and a pulmonary function test if
dyspnoea is the main symptom. Such tests can be done on an outpatient
basis.
Blood tests identify potential causes of ischaemia (e.g. severe anaemia,
hyperthyroidism), cardiovascular risk factors (e.g. lipids, fasting glucose),
and yield prognostic information (e.g. renal disease, inflammation).
A lipid profile, including total cholesterol, high-density lipoprotein
cholesterol (HDL-C), and triglycerides, allowing calculation of low-density
lipoprotein cholesterol (LDL-C), is necessary in every person with
suspected CCS to refine his/her risk profile and guide treatment.

Recommendations for history taking, risk factor assessment, and

resting electrocardiogram in individuals with suspected CCS

Recommendations Class Level

In individuals reporting symptoms of suspected myocardial

ischaemic origin, a detailed assessment of cardiovascular
risk factors, medical history, and symptom characteristics I C
(including onset, duration, type, location, triggers, relieving
factors, time of day) is recommended.

Symptoms like chest pain triggered by emotional stress;

dyspnoea or dizziness on exertion; pain in the arms, jaw,
IIa B
neck, or upper back; or fatigue should be considered as
potential angina equivalents.

If clinical or ECG assessment suggests ACS rather

than CCS, immediate referral to the emergency department
and/or repeated measurement of blood troponin, preferably I B
using high-sensitivity or ultrasensitive assays, to rule out
acute myocardial injury, is recommended.

14
A resting 12-lead ECG is recommended in all individuals
reporting chest pain (unless an obvious non-cardiac cause is
I C
identified), particularly during, or immediately after, an
episode suggestive of myocardial ischaemia.

Using ST-segment deviations during supraventricular

tachyarrhythmias, particularly during re-entrant
III B
atrioventricular tachycardias, per se, as reliable evidence of
obstructive CAD, is not recommended.
ACS, acute coronary syndrome; CAD, coronary artery disease; CCS, chronic
coronary syndrome; ECG, electrocardiogram.

Recommendations for basic biochemistry in the initial diagnostic

management of individuals with suspected CCS

Recommendations Class Level

The following blood tests are recommended in all individuals to refine risk
stratification, diagnose comorbidities, and guide treatment:

lipid profile including LDL-C; I A

full blood count (including haemoglobin); I B

creatinine with estimation of renal function; I B

glycaemic status with HbA1c and/or fasting plasma

I B
glucose.

In patients with suspected CCS, it is recommended to

I B
assess thyroid function at least once.

Additionally, hs-CRP and/or fibrinogen plasma levels

IIa B
should be considered.
CCS, chronic coronary syndrome; HbA1c, glycated haemoglobin; hs-CRP,
high-sensitivity C-reactive protein; LDL-C, low-density lipoprotein
cholesterol.

15
STEP 2: Further evaluation

Pre-test clinical likelihood of obstructive atherosclerotic

coronary artery disease

The 2019 ESC Guidelines for the diagnosis and management of chronic
coronary syndromes introduced the Clinical Likelihood concept as a more
comprehensive and individualized assessment of the pre-test probability
(PTP) of obstructive CAD.

Compared to a basic pre-test probability model (based on age, sex, and

symptoms), incorporation of risk factors leads to improved discrimination
of obstructive CAD at ICA, down-classifies more individuals to very low and
low likelihood of disease, and maintains high calibration. The Risk-Factor-
weighted Clinical Likelihood (RF-CL) model includes sex, age, angina
symptoms, and number of risk factors (Figure 4). The RF-CL model
increases three-fold the number of subjects categorized as at very low
(≤5%) likelihood of obstructive CAD compared with the 2019 ESC-PTP
model (38% vs. 12%), while predicting annualized event rates of MI and
death of 0.5%, 1.1%, and 2.1% for individuals having very low, low, and
moderate likelihood of obstructive CAD, respectively.

Coronary artery calcification can be assessed by measuring the coronary

artery calcium score (CACS) from an ECG-gated non-contrast CT scan or
qualitatively from a previous non-cardiac chest CT scan. CACS testing/
measuring should be considered in individuals with a low (5%-15%) RF-
CL pre-test likelihood. Combining CACS with the RF-CL model can allow
reclassifying these individuals to a very low (≤5%) CACS-weighted
likelihood, in whom deferring further cardiac testing should be considered
(Figure 5).

16
Figure 4 Estimation of the clinical likelihood of obstructive CAD

CAD, coronary artery disease; RF-CL, Risk factor-weighted clinical likelihood.

The numerical chest pain characteristic scale replaces the previous, potentially
misleading terminology, defining presence of three chest pain characteristic as
“typical” angina (here=3 points), two of three characteristics as “atypical” angina
(here=2 points), and no or one characteristic as ”non-cardiac/non-anginal“
(here=0–1 point). Family history of CAD is defined as 1 or more first-degree
relatives with early signs of CAD (men <55 and women <65 years of age);
smoking, as current or past smoker; dyslipidaemia, hypertension, and diabetes,
as present at the time of diagnosis. Values in the lower panel are the clinical
likelihood estimates expressed as %.
17
Figure 5 Adjustment and reclassification of the estimated
clinical likelihood of obstructive CAD

CACS, coronary artery calcium score using the Agatston method; CACS-CL,
coronary artery calcium score + RF-CL model; CAD, coronary artery disease;
CT, computed tomography; ECG, electrocardiogram; LV, left ventricular; RF-
CL, risk factor-weighted clinical likelihood.
18
Recommendations for estimating, adjusting and reclassifying the
likelihood of obstructive CAD in the initial diagnostic management of
individuals with suspected CCS

Recommendations Class Level

It is recommended to estimate the pre-test likelihood of

obstructive epicardial CAD using the Risk Factor-weighted I B
Clinical likelihood model.

It is recommended to use additional clinical data (e.g.

examination of peripheral arteries, resting ECG, resting
echocardiography, presence of vascular calcifications on
I C
previously performed imaging tests) to adjust the estimate
yielded by the Risk Factor-weighted Clinical Likelihood
model.

In individuals with a very low (≤5%) pre-test likelihood of

obstructive CAD, deferral of further diagnostic tests should IIa B
be considered.

In individuals with a low (>5%–15%) pre-test likelihood of

obstructive CAD, CACS testing should be considered to
IIa B
reclassify subjects and to identify more individuals with very
low (≤5%) CACS-weighted clinical likelihood.

In individuals with an initially low (>5%–15%) likelihood of

obstructive CAD, exercise ECG and detection of
IIb C
atherosclerotic disease in non-coronary arteries may be
considered to adjust the pre-test likelihood estimate.
CACS, coronary artery calcium score; CAD, coronary artery disease; CCS,
chronic coronary syndrome; ECG, electrocardiogram.

19
 Transthoracic echocardiography at rest

An echocardiographic study will provide important information about

cardiac function and anatomy. Patients with CCS often have preserved left
ventricular ejection fraction (LVEF). A decreased LV function and/or
regional wall motion abnormalities may increase the suspicion of
ischaemic myocardial damage, and a pattern of LV dysfunction following
the anatomical perfusion territory of the coronary arteries is typical in
patients who have already had a myocardial infarction (MI).
Recommendations for resting transthoracic ultrasound and magnetic
resonance imaging in the initial diagnostic management of individuals
with suspected CCS

Recommendations Class Level

A resting transthoracic echocardiogram is recommended to:

measure LVEF, volumes and diastolic function;
identify regional wall motion abnormalities;
identify non-coronary cardiac disease (e.g. hypertrophy,
I B
cardiomyopathy, valve disease, pericardial effusion);
assess right ventricular function and estimate systolic
pulmonary artery pressure;
to refine risk stratification and guide treatment.

CMR, if available, may be considered as an alternative

imaging test in individuals with inconclusive IIb C
echocardiographic evaluation.
CCS, chronic coronary syndrome; CMR, cardiac magnetic resonance; LVEF,
left ventricular ejection fraction.

20
 Exercise ECG testing
With low sensitivity (58%) and specificity (62%), exercise ECG testing has a low
diagnostic performance for detecting obstructive CAD and should mainly be
used for risk stratification. Nevertheless, it can still help objectify symptoms and
detect myocardial ischemia, even when obstructive epicardial CAD is absent.
Therefore, exercise ECG testing remains a valuable clinical tool, especially when
non-invasive imaging tests are unavailable.

Recommendations for exercise ECG in the initial diagnostic

management of individuals with suspected CCS
Recommendations Class Level

Exercise ECG is recommended in selected patients for the

assessment of exercise tolerance, symptoms, I C
arrhythmias,BP response, and event risk.

Exercise ECG may be considered as an alternative test to rule in

and rule out obstructive CAD when non-invasive imaging tests IIb B
are unavailable.

An exercise ECG may be considered to refine risk stratification

IIb B
and treatment.

In individuals with a low (>5%–15%) pre-test likelihood of

obstructive CAD, an exercise ECG may be considered to IIb C
identify patients in whom further testing can be deferred.

Exercise ECG is not recommended for diagnostic purposes in

patients with ≥0.1 mV ST-segment depression on resting ECG, III C
left bundle branch block or who are being treated with digitalis.

In individuals with a low or moderate pre-test likelihood of

obstructive CAD, an exercise ECG is not recommended to rule III C
out CAD if CCTA or functional imaging tests are available.
BP, blood pressure; CAD, coronary artery disease; CCS, chronic coronary
syndrome; CCTA, coronary computed tomography angiography; ECG,
electrocardiogram.

21
 Chest X-ray

Although chest X-ray is commonly performed to evaluate individuals

experiencing chest pain, in the context of CCS, it does not yield specific
information for accurate diagnosis or risk stratification.

Recommendation for chest X-ray in the initial diagnostic management

of individuals with suspected CCS

Recommendation Class Level

A chest X-ray should be considered for individuals with:

signs and symptoms suggestive of heart failure;
suspected acute pulmonary disease; IIa C
suspected aortic, non-coronary cardiac, or other thoracic
causes of chest pain.

Ambulatory ECG monitoring

Ambulatory ECG monitoring can assist in evaluating patients with chest

pain and palpitations. It can also help detect and evaluate silent myocardial
ischaemia, as well as in line with silent suspected vasospastic angina
(VSA).

Recommendations for ambulatory ECG monitoring in the initial

diagnostic management of individuals with suspected CCS

Recommendations Class Level

Ambulatory ECG monitoring is recommended in subjects

I C
with chest pain and suspected arrhythmias.

Ambulatory ECG monitoring should be considered in

IIa B
subjects with suspected vasospastic angina.
CCS, chronic coronary syndrome; ECG, electrocardiogram.

22
STEP 3: Confirming the diagnosis

Anatomical imaging: Coronary computed tomography

angiography (CCTA)

Through the intravenous injection of contrast agent, CCTA allows direct

anatomical visualization of the coronary artery lumen and
wall. CCTA offers a practical, non-invasive test with proven diagnostic
performance in detecting and ruling-out obstructive CAD.

Recommendations for non-invasive anatomical imaging tests in the

initial diagnostic management of individuals with
suspected CCS – CCTA, if available and supported by local expertise

Recommendations Class Level

In individuals with suspected CCS and low or moderate

(>5%–50%) pre-test likelihood of obstructive CAD, CCTA is
I A
recommended to diagnose obstructive CAD and to estimate
the risk of MACE.

CCTA is recommended in individuals with low or moderate

(>5%–50%) pre-test likelihood of obstructive CAD refine I B
diagnosis, if another non-invasive test is non-diagnostic.

CCTA is not recommended in patients with severe renal

failure (eGFR <30 mL/min/1.73 m2), decompensated heart
failure, extensive coronary calcification, fast irregular heart
III C
rate, severe obesity, inability to cooperate with breath-hold
commands, or any other conditions that can make obtaining
good imaging quality unlikely.
CAD, coronary artery disease; CCS, chronic coronary syndrome; CCTA,
coronary computed tomography angiography; eGFR, estimated glomerular
filtration rate; MACE, major adverse cardiovascular events.

23
 Functional imaging
Stress echocardiography detects myocardial ischaemia by assessing
regional systolic wall thickening abnormalities (RWTA) during stress. It
relies on inducing myocardial ischaemia by increasing myocardial oxygen
demand beyond the myocardial blood supply. Because ischaemia starts in
the subendocardium, which contributes to more than 50% of systolic
myocardial wall thickening, stress testing will precipitate wall thickening
abnormalities in the perfusion territory of narrowed coronary arteries.

Recommendations for non-invasive tests in the initial diagnostic

management of individuals with suspected CCS – stress
echocardiography, if available, and supported by local expertise

Recommendations Class Level

In individuals with suspected CCS and moderate or high

(>15%–85%) pre-test likelihood of obstructive CAD, stress
I B
echocardiography is recommended to diagnose myocardial
ischaemia and to estimate the risk of MACE.

During stress echocardiography, when two or more

contiguous myocardial segments are not visualized, it is
recommended to use commercially available intravenous I B
ultrasound contrast agents (microbubbles) to improve
diagnostic accuracy.

During stress echocardiography, myocardial perfusion using

commercially available intravenous ultrasound contrast
agents (microbubbles) is recommended to improve I B
diagnostic accuracy and to refine risk stratification beyond
wall motion.

During stress echocardiography, Doppler left anterior

descending coronary artery flow reserve may be considered
IIb B
to improve risk stratification beyond wall motion and to
assess microvascular function.
CAD, coronary artery disease; CCS, chronic coronary syndrome; MACE,
major adverse cardiovascular events.

24
Aside from providing highly accurate and reproducible assessments of
overall cardiac anatomy, cardiac volumes, function, and tissue
characterization, CMR also offers the ability to assess myocardial
perfusion, which relies on the first-pass myocardial perfusion of
gadolinium-based contrast agents.

Recommendations for non-invasive functional myocardial imaging tests

in the initial diagnostic management of individuals with
suspected CCS – stress SPECT/PET – CMR imaging, if available, and
supported by local expertise

Recommendations Class Level

In individuals with suspected CCS and moderate or high

(>15%–85%) pre-test likelihood of
obstructive CAD, SPECT or, preferably, PET myocardial
perfusion imaging is recommended to: I B
diagnose and quantify myocardial ischaemia and/or scar;
estimate the risk of MACE;
quantify myocardial blood flow (PET).

In patients selected for PET and for SPECT myocardial

perfusion imaging, it is recommended to
measure CACS from unenhanced chest CT imaging (used I B
for attenuation correction to improve detection of both non-
obstructive and obstructive CAD).

In individuals with suspected CCS and moderate or high

(>15%–85%) pre-test likelihood of
obstructive CAD, CMR perfusion imaging is recommended I B
to diagnose and quantify myocardial ischaemia and/or scar
and estimate the risk of MACE.
CACS, coronary artery calcium score; CAD, coronary artery disease; CCS,
chronic coronary syndrome; CMR, cardiac magnetic resonance; CT,
computed tomography; MACE, major adverse cardiovascular events; PET,
positron emission tomography; SPECT, single-photon emission computed
tomography.

25
 Invasive tests
Invasive coronary angiography (ICA) with available coronary pressure
assessment is indicated in patients with a very high (>85%) clinical
likelihood of obstructive CAD, in particular, those with severe symptoms
refractory to antianginal treatment, characteristic angina or dyspnoea at a
low level of exercise or left ventricle dysfunction suggesting extensive
obstructive CAD.

Recommendations for invasive coronary angiography in the diagnostic

management of individuals with suspected CCS

Recommendations Class Level

When ICA is indicated, radial artery access is recommended

I A
as the preferred access site.

When ICA is indicated, it is recommended to have coronary

pressure assessment available and to use it to evaluate the
I A
functional severity of intermediate non-left main stem
stenosesa prior to revascularization.

ICA is recommended to diagnose obstructive CAD in

individuals with a very high (>85%) clinical likelihood of
disease, severe symptoms refractory to guideline-directed I C
medical therapy, angina at a low level of exercise, and/or
high event risk.

In individuals with de novo symptoms highly suggestive of

obstructive CAD that occur at a low level of
exercise, ICA with a view towards revascularization is I C
recommended as first diagnostic test after a clinical
assessment by a cardiologist.

When ICA is indicated, measurement of FFR/iFR should be

considered to evaluate the functional severity of intermediate IIa A
left main stem stenosesa prior to revascularization.

26
When ICA is indicated, IVUS should be considered to
evaluate the severity of intermediate stenoses of left main IIa B
stema prior to revascularization.
CAD, coronary artery disease; FFR, fractional flow reserve; ICA, invasive
coronary angiography; iFR, instantaneous wave-free ratio; IVUS,
intravascular ultrasound.
a
Typically 40%-90% for non-left main stem stenoses and 40%-70% for left
main stem stenoses by visual estimate. For ICA in the diagnostic
management of individuals with suspected ANOCA/INOCA, see 4.2.
(specific groups).
When non-invasive stress tests are inconclusive or not performed,
identifying the artery responsible for ischaemia during ICA can be
challenging, especially in cases with multivessel CAD or coronary stenoses
of intermediate severity. In such cases, recording wire-based intracoronary
pressure during maximal hypaeremia to calculate FFR or at rest to
measure iFR is recommended to improve risk assessment and clinical
decision-making and to reduce clinical events.

Recommendations for functional assessment of epicardial artery

stenosis severity during invasive coronary angiography to guide
revascularization

Recommendations Class Level

During ICA, selective assessment of functional severity of

intermediatea diameter stenoses is recommended to guide the decision to
revascularize, using the following techniques:

FFR/iFR (significant ≤0.8 or ≤0.89, respectively); I A

QFR (significant ≤0.8). I B

In addition:

CFR/HSR/CFC should be considered as a complementary

IIa B
investigation;

27
 Resting invasive measurement of Pd/Pa, dPR, RFR, or
angiography-derived vessel FFR may be considered as IIb C
alternative parameters.

Systematic and routine wire-based coronary pressure

III A
assessment of all coronary vessels is not recommended.
CFC, coronary flow capacity; CFR, coronary flow reserve; dPR, diastolic
pressure ratio; FFR, fractional flow reserve; HSR, hyperaemic stenosis
resistance; ICA, invasive coronary angiography; iFR, instantaneous wave-
free ratio; Pd/Pa, distal coronary pressure to aortic pressure ratio; QFR,
quantitative flow ratio; RFR, relative flow reserve.
a
Typically around 40%–90% of non-left main stem or 40%–70% of left main
stem by visual estimate.

Diagnostic algorithm and selection of appropriate tests

After estimation of the pre-test likelihood of obstructive

epicardial CAD based on the RF-CL model (Figure 4 and Figure 5), further
diagnostic testing is dependent on the clinical scenario, general condition,
QoL, presence of comorbidities, local availability and expertise for different
diagnostic techniques, and importantly the patient expectations and
preferences (Figure 6; Table 3).

28
Figure 6 Appropriate first-line testing in symptomatic patients
with suspected CCS

CAD, coronary artery disease; CCS, chronic coronary syndrome; CCTA, coronary
computed tomography angiography; CMR, cardiac magnetic resonance; ECHO,
echocardiography; PET, positron emission tomography; SPECT, single-photon emission
computed tomography.
Functional imaging should be selected as a first line test if information on
myocardial ischaemia, viability, or microvascular disease is desired. Tests
for detecting ischaemia have better rule in power compared with CCTA and
should therefore be selected if there is a higher likelihood. Moreover, they
overcome the limitations of CCTA in certain patient groups, avoiding
exposure to ionizing radiation in young patients and in those with
suspected ANOCA/INOCA (Figure 7).

29
Figure 7 Initial management of symptomatic patients with
suspected CCS

ANOCA, angina with non-obstructive coronary arteries; CAD, coronary artery

disease; CCS, chronic coronary syndrome; CCTA, coronary computed
tomography angiography; CMR, cardiac magnetic resonance; Echo,
echocardiography; FFR, fractional flow reserve; ICFT, invasive coronary functional
testing; iFR, instantaneous wave-free ratio; INOCA, ischaemia with non-
obstructed coronary arteries; LV, left ventricular; PET, positron emission
tomography; SPECT, single-photon emission computed tomography. Consider
local availability and expertise, and patient characteristics, when choosing non-
invasive testing. Table 3 offers tips for selecting the first-line test in people with
suspected chronic coronary syndrome.

30
a
High-risk CAD: obstructive CAD on CCTA at high risk of adverse events:
≥50% stenosis of the left main stem; three-vessel disease with severe
stenoses (≥70% diameter stenosis); two-vessel disease including the
proximal LAD with severe stenoses. Consider functional imaging or
invasive investigation.

Many individuals in the moderate likelihood group will have a likelihood of

obstructive CAD around 20%. In these, both anatomical and functional
testing will result in an intermediate positive predictive value with
eventually many false positives, especially with CCTA easily overestimating
stenoses severity. Sequential testing; functional testing after CCTA, or vice
versa; will therefore be needed in many individuals to establish an accurate
diagnosis of obstructive, ischaemia-inducing CAD (Figure 8) before
considering coronary revascularization. Sequential or combined anatomical
and functional testing is also useful for the non-invasive diagnosis
of ANOCA/INOCA. Moreover, combined testing, e.g.
combining CCTA and PET, may result in improved prognostication
of CCS patients.
The curves in Figure 8 display the post-test likelihood of obstructive CAD in
the presence of a positive (+) or negative (−) CCTA or dobutamine stress
echocardiography (DSE) result, according to the pre-test likelihood of
obstructive CAD.
A 70-year-old woman with four coronary risk factors and exertional
dyspnoea has a pre-test likelihood of 16% (A, Figure 8). A
normal CCTA almost completely rules out obstructive CAD with a very
low post-test likelihood (2%).
A 55-year-old man with two coronary risk factors and all three anginal
symptom characteristics has a pre-test likelihood of 27% (B, Figure 8). An
abnormal CCTA brings the post-test likelihood to 40%, insufficient to rule
in obstructive CAD. Subsequent DSE brings the post-test likelihood to
82%. A normal CCTA instead effectively rules out obstructive CAD.
A 69-year-old man with four coronary risk factors and all three anginal
symptom characteristics has a clinically-adjusted pre-test likelihood of
60% (based on abnormalities on the resting ECG; C, Figure 8). A
positive DSE on its own has a high post-test likelihood (± 90%). A
negative DSE is associated with a 32% post-test likelihood. A normal
subsequent CCTA would allow ruling out obstructive CAD (<5% post-test
likelihood).

31
Figure 8 Ruling in and ruling out functionally significant
obstructive CAD by sequential anatomical (CCTA) and functional
(DSE) testing

CAD, coronary artery disease; CCTA, coronary computed tomography

angiography; DSE, dobutamine stress echocardiography.

32
Table 3 Overview of non-invasive tests used for first-line testing in
patients with suspected CCS

Main imaging Requirements Limitations

target(s) in CCS

Anatomical imaging

CCTA Atherosclerosis Iodinated Severely impaired kidney

(obstructive and contrast functiona Documented
non-obstructive) Radiation allergy to iodinated
in epicardial Premedication: contrast Tachyarrhythmia
coronary arteries -Beta-blockers refractory to beta-
or ivabradine blockade Irradiation (esp.
for heart rate young women)
control
-Nitroglycerine
for adequate
vasodilation

SPECT/ Atherosclerosis Radiation Irradiation (esp. young

CT coronary artery women)
PET/ calcium score
CT

Functional imaging

Stress LVEF and Poor Echo windows

Echo volumes

Wall motion Performed with Poor Echo windows

abnormalities exercise, Contraindications to
Myocardial dobutamine and stressor
perfusion vasodilators
Coronary flow Echo contrast to
reserve improve image
quality and
assess perfusion

33
 CMR LVEF and Non-CMR-compatible
volumes metal devices
Severe claustrophobia

MI (scar) Paramagnetic Non-CMR-compatible

contrast metal devices
Severe claustrophobia
Haemodialysis

Ischaemia/blood Vasodilator Non-CMR-compatible

flow stress + metal devices
paramagnetic Severe claustrophobia
contrast Contraindications to
stressor
Haemodialysis

Wall motion Inotropic stress Non-CMR-compatible

abnormalities (dobutamine) metal devices
Severe claustrophobia
Contraindication to
stressor

SPECT LVEF and Vasodilator or Contraindication to

volumes exercise stress stressor
Ischaemia/ Radioactive Irradiation (esp. young
viability tracer women)

PET LVEF and Vasodilator Contraindication to

volumes stress stressor
Ischaemia/blood Radioactive Irradiation (esp. young
flow tracer (13N- women)
Viability ammonia,15O-
water,82Rb)
CCS, chronic coronary syndrome; CCTA, coronary computed tomography angiography;
CMR, cardiac magnetic resonance; CT, computed tomography; Echo, echocardiography;
LVEF, left ventricular ejection fraction; MI, myocardial infarction; PET, positron emission
tomography; SPECT, single-photon emission computed tomography.
Preventive measures are recommended for patients with eGFR <30 mL/
a

min/1.73 m2.

34
Recommendations for selection of initial diagnostic tests in individuals
with suspected CCS

Recommendations Class Level

Selection of non-invasive testing

It is recommended to select the initial non-invasive

diagnostic test based on pre-test likelihood of
obstructive CAD, other patient characteristics that influence I C
the performance of non-invasive tests,a and local expertise
and availability.

In symptomatic patients in whom the pre-test likelihood of

obstructive CAD by clinical assessment is >5%, CCTA or
I B
non-invasive functional imaging for myocardial ischaemia is
recommended as the initial diagnostic test.

To rule out obstructive CAD in individuals with low or

moderate (>5%–50%) pre-test likelihood, CCTA is I B
recommended as the preferred diagnostic modality.

CCTA is recommended in individuals with low or moderate

(>5%–50%) pre-test likelihood if functional imaging for I B
myocardial ischaemia is not diagnostic.

Functional imaging for myocardial ischaemia is

recommended if CCTA has shown CAD of uncertain I B
functional significance or is not diagnostic.

In patients with known intermediate coronary artery

stenosisb in a proximal or mid coronary segment IIb B
on CCTA, CT-based FFR may be considered.

Subsequent invasive testing

Invasive coronary angiography with the availability of

invasive functional assessment is recommended to confirm
or exclude the diagnosis of obstructive CAD or ANOCA/ I B
INOCA in individuals with an uncertain diagnosis on non-
invasive testing.

35
ANOCA, angina with non-obstructive coronary arteries; CAD, coronary artery
disease; CCTA, coronary computed tomography angiography;
CT, computed tomography; FFR, fractional flow reserve; INOCA, ischaemia
with non-obstructive coronary arteries.
a
Characteristics determining ability to exercise, likelihood of good image
quality, expected radiation exposure, and risks or contraindications.
b
Typically around 40%–90% by visual estimate.

Adverse event risk assessment

To assess event risk, clinicians should choose an integrative approach,
considering risk factors, comorbidities, LV dysfunction, severity of
myocardial ischaemia, number of functionally significantly stenotic
coronary arteries, and coronary plaque burden and characteristics, as all of
these are prognostic.

Recommendations for definition of high risk of adverse events

Recommendations Class Level

An initial stratification of risk of adverse events is

recommended based on basic clinical assessment (e.g. I B
age, ECG, anginal threshold, diabetes, CKD, LVEF).

The use of one or more of the following test results is

recommended to identify individuals at high risk of adverse
events:
exercise ECG: Duke Treadmill Score ≤-10;
SPECT or PET perfusion imaging: area of ischaemia ≥10%
of the LV myocardium;
stress echocardiography: ≥3 of 16 segments with stress-
I B
induced hypokinesia or akinesia;
CMR: ≥2 of 16 segments with stress perfusion defects or ≥3
dobutamine-induced dysfunctional segments;
CCTA: ≥50% left main disease; ≥70% three-vessel disease
withproximal stenoses; ≥70% two-vessel disease, including
the proximal LAD; or ≥70% proximal LAD with FFR-
CT ≤0.8.

36
 In individuals at high risk of adverse events (regardless of
symptoms), ICA—complemented by invasive coronary
pressure (FFR/iFR) when appropriate—is recommended,
I A
with the aim of refining risk stratification and improving
symptoms and cardiovascular outcomes by
revascularization.
CCTA, coronary computed tomography angiography; CKD, chronic kidney
disease; CMR, cardiac magnetic resonance; CT, computed tomography;
ECG, electrocardiogram; FFR, fractional flow reserve; FFR-CT, CCTA-derived
FFR; ICA, invasive coronary angiography; iFR, instantaneous wave-free ratio;
LAD, left anterior descending; LV, left ventricular; LVEF, left ventricular
ejection fraction; PET, positron emission tomography; SPECT, single-
photon emission computed tomography.

STEP 4: Initial therapy

Guideline-directed therapy is started during or after the diagnostic process.

The main goals of treating CCS are to improve patients’ quality of life and
life expectancy. This includes reducing the risk of (1) cardiac mortality, (2)
non-fatal ischaemic events, (3) progression of epicardial and/or
microvascular chronic coronary disease, and (4) symptoms caused by CCS.
Treatment decisions should consider patient preferences, possible
complications, and healthcare costs. In shared decision-making with
patients, clinicians should clearly explain that certain treatments can
alleviate symptoms, while others can reduce the likelihood of ischaemic
events.

37
Guideline-directed therapy

Patient education, lifestyle optimization for risk

factor control, and exercise therapy

Recommendations for cardiovascular risk reduction, lifestyle changes,

and exercise interventions in patients with established CCS

Recommendations Class Level

An informed discussion on CVD risk and treatment benefits

I C
tailored to individual patient needs is recommended.

Multidisciplinary behavioural approaches to help patients

achieve healthy lifestyles, in addition to appropriate I A
pharmacological management, are recommended.

A multidisciplinary exercise-based programme to improve

cardiovascular risk profile and reduce cardiovascular I A
mortality is recommended.

Aerobic physical activity of at least 150–300 min per week of

moderate intensity or 75–150 min per week of vigorous I B
intensity and reduction in sedentary time are recommended.

Home-based cardiac rehabilitation and mobile health

interventions should be considered to increase patients’ long-
IIa B
term adherence to healthy behaviours, and to reduce
hospitalizations or cardiac events.
CVD, cardiovascular disease.

38
Table 4 Practical advice on lifestyle counselling and interventions

Topic Recommendation and treatment goals in patients

with established CCS

Lifestyle counselling

Immunization Vaccination against influenza, pneumococcal disease

and other widespread infections, eg COVID-19

Sleep quality Treat sleep-related breathing disorders

Sexual activity Males & females: low risk for stable patients that are
not symptomatic at low-to-moderate activity levels
Males: PDE-5 inhibitors are generally safe, not to be
taken in combination with nitrate medications
because of risk of severe hypotension

Psychosocial Avoid psychosocial stress

aspects Treat depression and anxiety by psychological or
pharmacological interventions

Environment/ Avoid passive smoking

pollution Reduce environmental noise
Avoid exposure to air pollution

Lifestyle interventions for risk factor control

Smoking and Use pharmacological and behavioural strategies to

substance abuse assist in smoking cessation
Avoid e-cigarettes
Abstain from substance abuse

Obesity and Obtain and maintain a healthy weight (BMI 18.5–25

overweight kg/m2)
Reduce weight through recommended energy intake
and increased physical activity and through
pharmacological/surgical interventions in selected
patients

39
Hyperlipidaemia Ultimate LDL-C goal of <1.4 mmol/L (55 mg/dL) and
a ≥50% reduction in LDL-C vs. baseline is
recommended

Diabetes HbA1c <7.0% (53 mmol/mol)

Arterial SBP 120–129 mmHg, provided the antihypertensive

hypertension treatment is well tolerated

Diet and alcohol Limit alcohol consumption <100 g/week

consumption Diet high in vegetables, fruit, and
wholegrains(Mediterranean diet)
Limit saturated fat to <10% of total calory intake

Physical activity 30–60 min moderate activity, >5 days/week

and exercise Reduce sedentary time and engage in at least light
activity throughout the day
BMI, body mass index; CCS, chronic coronary syndrome; COVID-19,
coronavirus disease-2019; HbA1c, glycated haemoglobin; LDL-C, low-
density lipoprotein cholesterol; PDE-5, phosphodiesterase-5; SBP, systolic
blood pressure.

40
Antianginal/anti-ischaemic medication

General strategy

For many patients with CCS, initial drug therapy should include a beta-
blocker and/or a calcium-channel blocker (CCB). Other antianginal drugs
(long-acting nitrates, ivabradine, nicorandil, ranolazine, trimetazidine) can
be added on top of a beta-blocker and/or a CCB, or as a part of initial
combination therapy in appropriately selected patients (Figure 9).

Regardless of the initial strategy, response to initial antianginal therapy

should be reassessed, and treatment should be adapted if adequate angina
control is not achieved or if the initial treatment is poorly tolerated.

Beta-blockers

Beta-blockers can be used for symptomatic relief of angina, or to improve

prognosis in some patients with CCS. If used for antianginal purposes, the
aim should be to lower resting heart rate to 55–60 beats per minute
(b.p.m.).

Combination therapy

If a combination of antianginal drugs is required, the selection of the most

appropriate drugs should be individualized and determined by the
haemodynamic profile, comorbidities, and tolerability (Figure 9).

41
Figure 9 Possible combinations of antianginal drugs

CAD, coronary artery disease; CCB, calcium channel blocker; COPD, chronic
obstructive pulmonary disease; HCM, hypertrophic cardiomyopathy; HFrEF,
heart failure with reduced ejection fraction.

The schematic shows useful combinations (green lines), combinations that

are not recommended (red lines), possible combinations (solid blue lines),
and drugs with similar effects (blue dashed lines) which can be combined
in selected indications: HFrEF (ivabradine and beta-blocker), atrial
fibrillation (diltiazem/verapamil and beta-blocker), vasospastic angina
(dihydropyridine CCB and nitrates).
42
Recommendations for antianginal drugs in patients with CCS

Recommendations Class Level

General strategy

It is recommended to tailor the selection of antianginal drugs

to the patient’s characteristics, comorbidities, concomitant
medications, treatment tolerability, and underlying I C
pathophysiology of angina, also considering local drug
availability and cost.

Selection of antianginal medication

Short-acting nitrates are recommended for immediate relief

I B
of angina.

Initial treatment with beta-blockers and/or CCBs to control

heart rate and symptoms is recommended for most patients I B
with CCS.a

If anginal symptoms are not successfully controlled by initial

treatment with a beta-blocker or a CCB alone, the
IIa B
combination of a beta-blocker and a DHP-CCB should be
considered, unless contraindicated.

Long-acting nitrates or ranolazine should be considered as

add-on therapy in patients with inadequate control of
symptoms while on treatment with beta-blockers and/or IIa B
CCBs, or as part of initial treatment in properly selected
patients.b

When long-acting nitrates are prescribed, a nitrate-free or

low-nitrate interval should be considered to reduce IIa B
tolerance.

Ivabradine should be considered as add-on antianginal

therapy in patients with left ventricular systolic dysfunction
IIa B
(LVEF <40%) and inadequate control of symptoms, or as
part of initial treatment in properly selected patients.

43
 Nicorandil or trimetazidine may be considered as add-on
therapy in patients with inadequate control of symptoms
IIb B
while on treatment with beta-blockers and/or CCBs, or as
part of initial treatment in properly selected patients.

Ivabradine is not recommended as add-on therapy in

patients with CCS, LVEF >40%, and no clinical heart III B
failure.

Combination of ivabradine with non-DHP-CCB or other

III B
strong CYP3A4 inhibitors is not recommended.

Nitrates are not recommended in patients with hypertrophic

cardiomyopathy or in co-administration with III B
phosphodiesterase inhibitors.
Legend Table of Recommendations
CCB, calcium channel blocker; CCS, chronic coronary syndrome; CYP3A4,
cytochrome P450 3A4; DHP, dihydropyridine; LVEF, left ventricular ejection
fraction.
a
These drugs may require caution or may be contraindicated in certain
patients with low blood pressure (beta-blockers and DHP-CCB), diabetes
mellitus (beta-blockers), atrioventricular conduction disorders (beta-
blockers and non-DHP-CCB), chronic obstructive pulmonary disease (non-
cardioselective beta-blockers).
b
Consideration for initial therapy: ivabradine, nicorandil, long-acting nitrates,
ranolazine, or trimetazidine for patients with intolerance to or
contraindications for beta-blockers and/or CCBs; trimetazidine and
ranolazine for patients with microvascular angina; nicorandil or nitrates for
patients with coronary artery spasm. The drugs are listed in alphabetical
order.

44
Medical therapy for event prevention

Antithrombotic drugs

Mechanisms of action. The mechanisms of action of the most commonly

used antithrombotic drugs in CCS patients are depicted in Figure 10.

Dual antiplatelet therapy (DAPT) post-percutaneous coronary intervention

(PCI). After PCI for CCS, DAPT consisting of aspirin and clopidogrel is
recommended for 6 months to reduce the risk of stent thrombosis
and MI compared to aspirin alone. The overall data indicate that,
in CCS patients with high bleeding risk (HBR), DAPT discontinuation 1–3
months after PCI is recommended, while in patients without
HBR, DAPT duration may be reduced only in the absence of high ischaemic
risk (Figure 11).

Recommendations for antithrombotic therapy in patients with CCS

Recommendations Class Level

In CCS patients with a prior MI or remote PCI, aspirin 75–

100 mg daily is recommended lifelong after an initial period I A
of DAPT.

In CCS patients with a prior MI or remote PCI, clopidogrel

75 mg daily is recommended as a safe and effective I A
alternative to aspirin monotherapy.

After CABG, aspirin 75–100 mg daily is recommended

I A
lifelong.

In patients without prior MI or revascularization but with

evidence of significant obstructive CAD, aspirin 75–100 mg I B
daily is recommended lifelong.

45
 Adding a second antithrombotic agent to aspirin for
extended long-term secondary prevention should be
IIa A
considered in patients at enhanced ischaemic riska and
without high bleeding risk.b

In CCS or stabilized post-ACS patients who

underwent PCI and were initially treated with ticagrelor-
based DAPT, who remain at high ischaemic riskc and are not
IIb C
at high bleeding risk, ticagrelor monotherapy 90
mg b.i.d. may be considered as an alternative to dual or
other single antiplatelet therapy.
ACS, acute coronary syndrome; b.i.d., bis in die (twice daily); CABG,
coronary artery bypass grafting; CAD, coronary artery disease; CCS, chronic
coronary syndrome; CYP2C19, cytochrome P450 2C19; DAPT, dual
antiplatelet therapy; INR, international normalized ratio; LAD, left anterior
descending; MI, myocardial infarction; OAC, oral anticoagulant; PCI,
percutaneous coronary intervention; VKA, vitamin K antagonist.
a
Enhanced ischaemic risk criteria for extended treatment with a second
antithrombotic agent. Risk factors for CCS (that may also apply to CABG)
patients include stenting of left main stem, proximal LAD, or last remaining
patent artery; suboptimal stent deployment; stent length >60 mm; diabetes
mellitus; CKD; bifurcation with two stents implanted; treatment of chronic
total occlusion; and previous stent thrombosis on adequate antithrombotic
therapy.
b
Bleeding risk criteria according to PRECISE-DAPT or ARC-HBR
c
For instance, for anatomical/procedural thrombotic risk characteristics:
stenting of left main, proximal LAD, or last remaining patent artery;
suboptimal stent deployment; stent length >60 mm; bifurcation with two
stents implanted; treatment of chronic total occlusions.

46
Figure 10 Antithrombotic drugs for CCS: mechanisms of action

47
ADP, adenosine diphosphate; FVIIa, activated factor VII; FXa, activated
factor X; GP, glycoproteïn; PAR, protease-activated receptor; TF, tissue
factor; TxA 2 , thromboxane A2; UFH, unfractionated heparin; VKA, vitamin K
antagonist. Orally administered drugs are shown on a blue background, the
parenterally administered ones on red. Aspirin prevents TxA 2 formation by
acetylating platelet cyclooxygenase-1.

48
Figure 11 Antithrombotic treatment for CCS patients
undergoing PCI

b.i.d., bis in die (twice daily); CCS, chronic coronary syndrome; CYP2C19,
cytochrome P450 2C19; DAPT, dual antiplatelet therapy; mo., months; OAC, oral
anticoagulant; o.d., once daily; PCI, percutaneous coronary intervention.
a
In CCS patients with high ischaemic risk, or known CYP2C19 *2/*3
polymorphisms, prasugrel or ticagrelor (in addition to aspirin) may be considered,
instead of clopidogrel, for the first month, and up to 3-6 months
b
Prasugrel 5 mg o.d. for patients aged ≥75 years or with a body weight <60 Kg.
Bleeding risk criteria according to PRECISE-DAPT or ARC-HBR.

49
 Table 5 Options for extended intensified antithrombotic therapy

ACS, acute coronary syndrome; BARC, Bleeding Academic Research Consortium; b.i.d., bis in die
(twice daily); CAD, coronary artery disease; DAPT, dual antiplatelet therapy; GUSTO, Global
Utilization of Streptokinase and Tissue Plasminogen Activator for Occluded Arteries; ISTH,
International Society on Thrombosis and Haemostasis; MI, myocardial infarction; NNH, number
needed to cause a harmful event; NNT, number needed to treat to prevent an adverse event;
o.d., once daily; PAD, peripheral artery disease; PCI, percutaneous coronary intervention. Drugs
(in addition to aspirin 75–100 mg/day) for extended DAPT options are listed in alphabetical
order. For definitions of highly/moderately increased ischaemic and bleeding risk see
Supplementary data online. NNT refers to the primary ischaemic endpoints and NNH refers to
the key safety endpoints of the respective trials. NNT and NNH from the DAPT trial are pooled
numbers for clopidogrel and prasugrel.

50
 Lipid-lowering drugs
Evidence from genetic, epidemiologic, and randomized clinical studies has
established the key causal role of LDL-C and other apo-B-containing
lipoproteins in the development of atherosclerotic disease.

Recommendations for lipid-lowering drugs in patients with CCS

Recommendations Class Level

Lipid-lowering treatment with an LDL-C goal of <1.4 mmol/

L (55 mg/dL) and a ≥50% reduction in LDL-C vs. baseline is I A
recommended.

A high-intensity statin up to the highest tolerated dose to

reach the LDL-C goals is recommended for all patients I A
with CCS.

If a patient’s goal is not achieved with the maximum

tolerated dose of statin, combination with ezetimibe is I B
recommended.

For patients who are statin intolerant and do not achieve

their goal on ezetimibe, combination with bempedoic acid is I B
recommended.

For patients who do not achieve their goal on a maximum

tolerated dose of statin and ezetimibe, combination with I A
a PCSK9 inhibitor is recommended.

For patients who do not achieve their goal on a maximum

tolerated dose of statin and ezetimibe, combination with IIa C
bempedoic acid should be considered.

For patients with a recurrent atherothrombotic event (not

necessarily of the same type as the first event) while taking
IIb B
maximally tolerated statin therapy, an LDL-C goal of <1.0
mmol/L (<40 mg/dL) may be considered.
CCS, chronic coronary syndrome; LDL-C, low-density lipoprotein
cholesterol; PCSK9, proprotein convertase subtilisin/kexin type 9.

51
 Sodium–glucose cotransporter 2 inhibitors and
glucagon-like peptide-1 receptor agonists

Recommendations for SGLT2 inhibitors or/and GLP-1 receptor agonists

in patients with CCS

Recommendations Class Level

CCS patients with type 2 diabetes

SGLT2 inhibitors with proven CV benefita are

recommended in patients with T2DM and CCS to
reduce CV events, independent of baseline or I A
target HbA1c and independent of concomitant glucose-
lowering medication.

GLP-1 receptor agonists with proven CV benefitb are

recommended in patients with T2DM and CCS to
reduce CV events, independent of baseline or I A
target HbA1c and independent of concomitant glucose-
lowering medication.

CCS patients without type 2 diabetes

The GLP-1 receptor agonist semaglutide should be

considered in CCS patients without diabetes who are
IIa B
overweight or obese (BMI >27 kg/m2), to
reduce CV mortality, MI, or stroke.
BMI, body mass index; CCS, chronic coronary syndrome; CV,
cardiovascular; GLP-1, glucagon-like peptide-1; HbA1c, glycated
haemoglobin; MI, myocardial infarction; SGLT2, sodium–glucose
cotransporter 2; T2DM, type 2 diabetes mellitus.
a
Canagliflozin, dapagliflozin, empagliglozin, sotagliflozin.bDulaglutide,
efpeglenatide, liraglutide, semaglutide. Listed in alphabetical order.

52
 Anti-inflammatory agents for event prevention

Recommendation for anti-inflammatory drugs in patients with CCS

Recommendation Class Level

In CCS patients with atherosclerotic CAD, low-dose

colchicine (0.5 mg daily) should be considered to reduce
IIa A
myocardial infarction, stroke, and need for
revascularization.
CAD, coronary artery disease; CCS, chronic coronary syndrome.

Recommendations for angiotensin-converting enzyme inhibitors in

patients with CCS

Recommendations Class Level

In CCS patients, ACE-Is (or ARBs) are recommended in the

presence of specific comorbidities, such as hypertension, I A
diabetes, or heart failure.

ACE-Is should be considered in CCS patients at very high

IIa A
risk of cardiovascular events.
ACE-I, angiotensin-converting enzyme inhibitor; ARB, angiotensin receptor
blocker; CCS, chronic coronary syndrome.

53
Revascularization for chronic coronary syndromes

Overview

Invasive treatment of CAD with either CABG or PCI is historically described

under the term revascularization. Although both procedures increase
coronary flow capacity and prevent myocardial ischaemia during exercise
or emotional stress, they do not heal coronary atherosclerosis.

Revascularization indications and modalities

Both myocardial revascularization modalities—PCI and CABG—can achieve

excellent outcomes, although through different mechanisms, in
appropriately selected patients when guideline-directed medical treatment
(GDMT) alone fails.

Patient–physician shared decision-making to perform and

select revascularization modality

Shared decision-making between patients and healthcare professionals,

based on the practice of patient-centred care, should be considered a
paramount process in defining the appropriate therapeutic pathway. While
the Heart Team decision is mainly driven by long-term survival benefits
with a certain modality of revascularization, patient’s preferences must be
respected.

Institutional protocols, clinical pathways, and quality of care

Institutional protocols, developed by the Heart Team and aligned with the
current Guidelines, should delineate specific anatomical and functional
criteria on disease complexity and clinical subsets defining patients’ risk
for cardiac surgery or PCI. The tables below provide guidance on the use of
revascularization to improve the outcomes and/or symptoms
of CCS patients. Further information can be found in the full guideline
document.

54
Recommendations for revascularization in patients with CCS

Recommendations Class Level

Informed and shared decisions

It is recommended that patients scheduled for percutaneous

or surgical revascularization receive complete information
about the benefits, risks, therapeutic consequences, and I C
alternatives to revascularization, as part of shared clinical
decision-making.

For complex clinical cases, to define optimal treatment

strategy, in particular when CABG and PCI hold the same
level of recommendation, a Heart Team discussion is
recommended, including representatives from interventional
I C
cardiology, cardiac surgery, non-interventional cardiology,
and other specialties if indicated, aimed at selecting the most
appropriate treatment to improve patient outcomes and
quality of life.

It is recommended to communicate the proposal of the Heart

Team in a very balanced way and in a language that the I C
patient can understand.

It is recommended that the decision for revascularization

and its modality be patient-centred, considering when
I C
possible patient preferences, health literacy, cultural
circumstances, and social support.

It is recommended that the Heart Team (on site or with a

partner institution) develop institutional protocols to
I C
implement the appropriate revascularization strategy in
accordance with current guidelines.

55
Revascularization to improve outcomes

In chronic coronary syndrome patients with left ventricular ejection

fraction >35%, myocardial revascularization is recommended, in addition
to guideline-directed medical therapy for patients:

with functionally significant left main stem stenosis to improve

I A
survival;

with functionally significant three-vessel disease to improve long-

term survival and to reduce long-term cardiovascular mortality I A
and the risk of spontaneous myocardial infarction;

with functionally significant single- or two-vessel disease involving

the proximal LAD, to reduce long-term cardiovascular mortality I B
and the risk of spontaneous myocardial infarction.

In CCS patients with LVEF ≤35%, it is recommended to choose

between revascularization or medical therapy alone, after careful
evaluation, preferably by the Heart Team, of coronary anatomy,
I C
correlation between coronary artery disease and LV dysfunction,
comorbidities, life expectancy, individual risk-to-benefit ratio, and
patient perspectives.

In surgically eligible CCS patients with

multivessel CAD and LVEF ≤35%, myocardial revascularization
I B
with CABG is recommended over medical therapy alone to improve
long-term survival.

In selected CCS patients with functionally

significant MVD and LVEF ≤35% who are at high surgical risk or IIb B
not operable, PCI may be considered as an alternative to CABG.

Revascularization to improve symptoms

In CCS patients with persistent angina or anginal equivalent,

despite guideline-directed medical treatment, myocardial
I A
revascularization of functionally significant obstructive CAD is
recommended to improve symptoms.

56
 Assessment of procedural risks and post-procedural outcomes

In patients with complex CAD in whom revascularization is being

considered, it is recommended to assess procedural risks and post- I C
procedural outcomes to assist in shared clinical decision-making.

Calculation of the STS score is recommended to estimate in-hospital

I B
morbidity and 30-day mortality after CABG.

In patients with multivessel obstructive CAD, calculation of

the SYNTAX score is recommended to assess the anatomical I B
complexity of disease.

Intracoronary imaging guidance by IVUS or OCT is recommended

for performing PCI on anatomically complex lesions, in particular I A
left main, true bifurcation, and long lesions.

Intracoronary pressure measurement (FFR or iFR) or computation (QFR)

is recommended to guide lesion selection for intervention in

I A
patients with multivessel disease;

should be considered at the end of the procedure to identify

patients at high risk of persistent angina and subsequent clinical IIa B
events;

may be considered at the end of the procedure to identify lesions

IIb B
potentially amenable to treatment with additional PCI.

Choice of revascularization modality

It is recommended that physicians select the most appropriate

revascularization modality based on the patient’s profile,a coronary
I C
anatomy,b procedural factors,c LVEF, preferences and outcome
expectations.
CABG, coronary artery bypass grafting; CAD, coronary artery disease; CCS,
chronic coronary syndrome; FFR, fractional flow reserve; iFR, instantaneous
wave-free ratio; IVUS, intravascular ultrasound; LAD, left anterior descending; LV,
left ventricular; LVEF, left ventricular ejection fraction; MVD, multivessel disease;
OCT, optical coherence tomography; PCI, percutaneous coronary intervention;

57
QFR, quantitative flow ratio; STS, Society of Thoracic Surgeons; SYNTAX,
SYNergy Between PCI With TAXUS and Cardiac Surgery.
a
Age, frailty, cognitive status, diabetes, and any other comorbidities.bMultivessel
disease with/out left main stem involvement, high anatomical complexity, and
likelihood of revascularization completeness.cLocal expertise and outcomes,
surgical and interventional risk.

Recommendations for mode of revascularization in patients with CCS

Recommendations Class Level

Anatomically and clinically based recommendations for

revascularization in CCS

Left main disease

In CCS patients at low surgical riska with significant left main coronary
stenosis, CABG:

is recommended over medical therapy alone to improve

I A
survival;

is recommended as the overall preferred revascularization

mode over PCI, given the lower risk of spontaneous I A
myocardial infarction and repeat revascularization.

In CCS patients with significant left main coronary stenosis

of low complexity (SYNTAX score ≤22), in whom PCI can
provide equivalent completeness of revascularization to that I A
of CABG, PCI is recommended as an alternative to CABG,
given its lower invasiveness and non-inferior survival.

In CCS patients with significant left main coronary stenosis

of intermediate complexity (SYNTAX score 23–32), in
whom PCI can provide equivalent completeness of
IIa A
revascularization to that of CABG, PCI should be
considered, given its lower invasiveness and non-inferior
survival.

58
Left main with multivessel diseaseb

In CCS patients at low surgical risk with suitable

anatomy, CABG is recommended over medical therapy alone to I A
improve survival.

In CCS patients at high surgical risk, PCI may be considered over

IIb B
medical therapy alone.

Multivessel diseaseb and diabetes

In CCS patients with significant multivessel disease and diabetes,

with insufficient response to guideline-directed medical
I A
therapy, CABG is recommended over medical therapy alone and
over PCI to improve symptoms and outcomes.

In CCS patients at very high surgical risk, PCI should be

considered over medical therapy alone to reduce symptoms and IIa B
adverse outcomes.

Three-vessel disease, without diabetes

In CCS patients with significant three-vessel disease,

preserved LVEF, no diabetes, and insufficient response to guideline-
I A
directed medical therapy, CABG is recommended over medical
therapy alone to improve symptoms, survival, and other outcomes.

In CCS patients with preserved LVEF, no diabetes, insufficient

response to guideline-directed medical therapy, and significant
three-vessel disease of low-to-intermediate anatomic complexity in
I A
whom PCI can provide similar completeness of revascularization to
that of CABG, PCI is recommended, given its lower invasiveness,
and generally non-inferior survival.

Single- or double-vessel disease involving the proximal LAD

In CCS patients with significant single- or double-vessel disease

involving the proximal LAD and insufficient response to guideline-
I A
directed medical therapy, CABG or PCI is recommended over
medical therapy alone to improve symptoms and outcomes.

59
 In CCS patients with complex significant single- or double-vessel
disease involving the proximal LAD, less amenable to PCI, and
insufficient response to guideline-directed medical I B
therapy, CABG is recommended to improve symptoms and reduce
revascularization rates.

Single- or double-vessel disease not involving the proximal LAD

In symptomatic CCS patients with significant single- or double-

vessel disease not involving the proximal LAD and with insufficient
I B
response to guideline-directed medical therapy, PCI is
recommended to improve symptoms.

In symptomatic CCS patients with significant single- or double-

vessel disease not involving the proximal LAD and with insufficient
response to guideline-directed medical therapy, not amenable to IIb C
revascularization by PCI, CABG may be considered to improve
symptoms.
CABG, coronary artery bypass grafting; CCS, chronic coronary syndrome;
LAD, left anterior descending; LVEF, left ventricular ejection fraction; PCI,
percutaneous coronary intervention; SYNTAX, SYNergy Between PCI With
TAXUS and Cardiac Surgery.
a
For example: absence of previous cardiac surgery, severe morbidities,
frailty, or immobility precluding CABG.
b
Multivessel disease is defined as the involvement of at least two main
coronary arteries.

60
Optimal assessment and treatment of specific
groups

Heart failure

Recommendations for the management of CCS patients with chronic

heart failure

Recommendations Class Level

Managing CCS in heart failure patients

In HF patients with LVEF ≤35% in whom

obstructive CAD is suspected, ICA is recommended with a
I B
view towards improving prognosis by CABG, taking into
account the risk-to-benefit ratio of the procedures.

In HF patients with LVEF >35% and suspected CCS with

low or moderate (>5%–50%) pre-test likelihood of
I C
obstructive CAD, CCTA or functional imaging is
recommended.

In HF patients with LVEF >35% and suspected CCS with

very high (>85%) pre-test likelihood of
I C
obstructive CAD, ICA (with FFR, iFR, or QFR when
needed) is recommended.

In patients with HFpEF with angina or equivalent symptoms

and normal or non-obstructive epicardial coronary
arteries, PET or CMR perfusion or invasive coronary IIa B
functional testing should be considered to detect or rule out
coronary microvascular dysfunction.

In selected patients with HFrEF undergoing high-

risk PCI for complex CAD, the use of a microaxial flow IIb C
pump may be considered in experienced centres.

61
CABG, coronary artery bypass grafting; CAD, coronary artery disease; CCS,
chronic coronary syndrome; CCTA, coronary computed tomography
angiography; CMR, cardiac magnetic resonance; FFR, fractional flow
reserve; HF, heart failure; HFpEF, heart failure with preserved ejection
fraction; HFrEF, heart failure with reduced ejection fraction; ICA, invasive
coronary angiography; iFR, instantaneous wave-free ratio; LVEF, left
ventricular ejection fraction; PCI, percutaneous coronary intervention; PET,
positron emission tomography; QFR, quantitative flow ratio.

Angina/ischaemia with non-obstructive coronary

arteries (ANOCA/INOCA)

Definition

A large proportion of patients undergoing coronary angiography because of

angina do not have obstructive epicardial coronary arteries (ANOCA). In
these patients, the prevalence of demonstrable ischaemia (INOCA) varies,
depending on the stress test performed, between 10%–30% (Figure 12).
Invasive coronary functional testing (ICFT) using acetylcholine (Ach) and
adenosine enables the differentiation of the following endotypes: (i)
endothelial dysfunction; (ii) impaired vasodilation (low coronary flow
reserve and/or high microvascular resistance); (iii) epicardial vasospastic
angina; (iv) microvascular vasospastic angina; (v) endotype combinations;
(vi) equivocal response, i.e. angina without fulfilling any endotype criteria.

62
Figure 12 Prevalence of disease characteristics in patients
with ANOCA/INOCA referred for invasive coronary functional
testing

Ach, acetylcholine; ANOCA, angina with non-obstructive coronary arteries;

CFR, coronary flow reserve; INOCA, ischaemia with non-obstructive
coronary arteries. In the ILIAS (Inclusive Invasive Physiological Assessment
in Angina Syndromes) registry, ANOCA is present in up to 70% of patients
referred for invasive coronary angiography and functional testing. The
prevalence of coronary vasospasm can vary in different studies depending
on the dose of acetylcholine and test protocol.
a
Prevalence of ischaemia by non-invasive functional testing increases
from non-obstructive to obstructive CAD.

63
 Diagnosis
The presence of myocardial ischaemia on functional imaging or on Holter ECG and of
non-obstructive CAD on CCTA or ICA should raise the clinical suspicion of ANOCA/
INOCA. A current comprehensive diagnosis of ANOCA/INOCA includes an invasive
functional evaluation of the coronary circulation (Figure 13 and Figure 14).

Figure 13 Diagnostic algorithm for patients with ANOCA/INOCA

64
Ach, acetylcholine; ANOCA, angina with non-obstructive coronary arteries;
CAD, coronary artery disease; CCS, chronic coronary syndrome; CCTA,
coronary computed tomography angiography; CFR, coronary flow reserve;
ECG, electrocardiogram; echo, echocardiography; FFR, fractional flow
reserve; GDMT, guideline-directed medical therapy; HMR, hyperaemic
microvascular resistance; i.c., intracoronary; ICA, invasive coronary
angiography; iFR, instantaneous-wave free ratio; IMR, index of
microcirculatory resistance; INOCA, ischaemia with non-obstructive
coronary arteries; MRI, magnetic resonance imaging; PET, positron
emission tomography; SPECT, single-photon emission computed
tomography.

Intracoronary pressure and flow measurements allow the assessment of:

(i) the haemodynamic significance of focal or diffuse coronary lesions, by
measuring FFR or iFR, and (ii) the microcirculatory function by
measuring CFR and microvascular resistance. Coronary microvascular
dysfunction (CMD) is characterized by decreased CFR and increased
microvascular resistance (IMR, HMR, MRR).
Figure 14 shows a standardized algorithm for diagnosing vasospasm and
microvascular function. Informed consent should be obtained, mentioning
unlicensed, parenteral use of Ach.

65
Figure 14 Spasm provocation and functional testing protocol

Ach, acetylcholine; CCB, calcium channel blocker; CFR, coronary flow

reserve; ECG, electrocardiogram; i.c., intracoronary; MR, microvascular
resistance; NTG, nitroglycerin. I.c. bolus injections of Ach over 60 s to
assess: (i) endothelial-dependent vasodilation (2–20 µg), and (ii)
endothelial dysfunction and vasoconstriction using high-dose (100–200
µg). These are followed by i.c. administration of NTG (200 µg) to revert
vasospasm. Endothelial-independent vasodilation is assessed
by i.c. adenosine (200 µg) to determine CFR and IMR. Coronary flow can be
continuously monitored if i.c. Doppler guidewires are used.
a
The incremental administration of Ach is stopped whenever coronary
vasospasm is induced.
b
IV adenosine infusion can also be used.

66
 Management of angina/ischaemia with non-obstructive
coronary arteries (ANOCA/INOCA)
A comprehensive algorithm for managing ANOCA/INOCA patients, including antianginal
treatment according to underlying endotypes, is shown in Figure 15. Of note, endotypes
frequently overlap, requiring combined medical therapy.

Figure 15 Treatment of ANOCA/INOCA

ACEi, angiotensin-converting enzyme inhibitor; ANOCA, angina with non-obstructive coronary

arteries; CCB, calcium channel blocker; INOCA, ischaemia with non-obstructive coronary
arteries.

67
Recommendations for diagnosis and management of patients
with ANOCA/INOCA

Recommendations Class Level

Diagnosis of ANOCA/INOCA endotypes

In persistently symptomatic patients despite medical

treatment with suspected ANOCA/INOCA (i.e. anginal
symptoms with normal coronary arteries or non-obstructive
lesions at non-invasive imaging, or intermediate stenoses
with normal iFR/FFR at coronary arteriography) and poor I B
quality of life, invasive coronary functional testing is
recommended to identify potentially treatable endotypes and
to improve symptoms and quality of life, considering patient
choices and preferences.

In persistently symptomatic patients with documented or

suspected ANOCA/INOCA, transthoracic Doppler of
the LAD, stress echocardiography, CMR, and PET may be IIb B
considered for the non-invasive assessment of coronary/
myocardial flow reserve.

Diagnostic tests for vasospastic angina

In individuals with suspected vasospastic angina, a resting

I C
12-lead ECG recording during angina is recommended.

In patients with suspected vasospastic angina and repetitive

episodes of rest angina associated with ST-segment changes
that resolve with nitrates and/or calcium antagonists,
I C
invasive coronary functional testing is recommended to
confirm the diagnosis and to determine the severity of
underlying atherosclerotic disease.

In individuals with suspected vasospastic angina and

frequent symptoms, ambulatory ST-segment monitoring
IIa B
should be considered to identify ST-segment deviation
during angina.

68
Medical management of ANOCA/INOCA

In symptomatic patients with ANOCA/INOCA, medical therapy

based on coronary functional test results should be considered to IIa A
improve symptoms and quality of life.

For the management of endothelial dysfunction, ACE-I should be

IIa B
considered for symptom control.

For the management of microvascular angina associated with

reduced coronary/myocardial blood flow reserve, antianginal
IIa B
medications aiming at preventing demand myocardial ischaemia
should be considered for symptom control.

For the treatment of isolated vasospastic angina

Calcium channel blockers are recommended to control symptoms

I A
and to prevent ischaemia and potentially fatal complications.

Nitrates should be considered to prevent recurrent episodes. IIa B

For the treatment of overlapping endotypes

In patients with evidence of overlapping endotypes, combination

therapy with nitrates, calcium channel blockers, and other IIb B
vasodilators may be considered.
ACE-I, angiotensin-converting enzyme inhibitor; ANOCA, angina with non-
obstructive coronary arteries; CMR, cardiac magnetic resonance; ECG,
electrocardiogram; FFR, fractional flow reserve; iFR, instantaneous wave-
free ratio; INOCA, ischaemia with non-obstructive coronary arteries; LAD,
left anterior descending; PET, positron emission tomography.

69
Other specific patient groups

Recommendations for older, female, high bleeding risk, comorbid, and

socially/geographically diverse patients

Recommendations Class Level

Older adults

In older adults (≥ 75 years), particular attention to drug side

effects, intolerance, drug–drug interactions, overdosing, and I C
procedural complications is recommended.

In older, as in younger, individuals, diagnostic and

revascularization decisions based on symptoms, extent of
I C
ischaemia, frailty, life expectancy, comorbidities, and patient
preferences are recommended.

Sex

Similar guideline-directed cardiovascular preventive therapy

I C
is recommended in women and men.

Systemic post-menopausal hormone therapy is not

recommended in women with CCS, given the lack of
III A
cardiovascular benefit and an increased risk of thrombo-
embolic complications.

High bleeding risk

Bleeding risk assessment is recommended using the

PRECISE-DAPT score, the qualitative ARC-HBR tool or I B
other, validated methods.

HIV

Attention to interaction between antiretroviral treatment

I B
and statins is recommended in patients with HIV.

70
Socioeconomic, geographical, and under-investigated groups

Continued targeted efforts are recommended:

to increase delivery of safe and effective cardiac care to
all CCS patients, especially those of lower socioeconomic classes;
I C
and
to enhance inclusion in future clinical trials of geographical, social, or
other groups that are currently underrepresented.
ARC-HBR, Academic Research Consortium for High Bleeding Risk; CCS,
chronic coronary syndrome; HIV, human immunodeficiency virus; PRECISE-
DAPT, PREdicting bleeding Complications In patients undergoing Stent
implantation and subsEquent Dual Anti Platelet Therapy.

71
Screening for coronary artery disease in
asymptomatic individuals

Recommendations for screening for coronary artery disease in

asymptomatic individuals

Recommendations Class Level

Opportunistic screening of healthy individuals for

cardiovascular risk factors and to estimate risk of future
cardiovascular events using scoring systems, I C
e.g. SCORE2 and SCORE-OP, is recommended to detect
individuals at high risk and guide treatment decisions.

When coronary artery calcification findings are available

from previous chest CT scans, using these findings to
IIa C
enhance risk stratification and guide treatment of modifiable
risk factors should be considered.

CACS may be considered to improve risk classification

IIb C
around treatment decision thresholds.

An ultrasound of the carotid arteries may be considered as

an alternative to CACS, when CACS is unavailable or not
IIb B
feasible, to detect atherosclerotic disease and to improve risk
classification around treatment decision thresholds.
CACS, coronary artery calcium scoring; CT, computed tomography;
SCORE2, Systematic Coronary Risk Estimation 2; SCORE-OP, Systematic
Coronary Risk Estimation 2-Older Persons.

72
Long-term follow-up and adherence

Overview
The five dimensions of adherence are patient, disease, provider, therapy, and healthcare system
(Figure 16). Therefore, essential steps include identifying patients at risk of non-adherence,
addressing all five dimensions, developing a multidisciplinary pathway to support sustained
adherence, and a follow-up strategy.
Figure 16 Actions on the five dimensions of adherence to therapy

e-Health, healthcare services provided electronically; mHealth, mobile device-based healthcare;

PROMs, patient-reported outcome measures.

73
 Adherence and persistence

Adherence to healthy lifestyle behaviours

Different strategies have been shown to improve long-term adherence to a healthy
lifestyle (Figure 17).
Figure 17 Strategies for long-term adherence to a healthy lifestyle

mHealth, mobile device-based healthcare; PROMs, patient-reported outcome measures.

74
 Adherence to medical therapy

Effective management of CCS and prevention of cardiovascular events

depend, at least in part, on a persisting adherence of patients to guideline-
directed medications. Despite robust evidence of benefits, in terms of
mortality and morbidity, adherence to guideline-directed medical therapy
remains suboptimal.

Recommendations for adherence to medical therapy and lifestyle

changes

Recommendations Class Level

Mobile health interventions (e.g. using text messages, apps,

wearable devices) are recommended to improve patient I A
adherence to healthy lifestyles and medical therapy.

Behavioural interventions are recommended to improve

I B
adherence.

Simplifying medication regimens (e.g. using fixed-dose drug

combinations) is recommended to increase patient adherence I B
to medications.

Multiprofessional and family involvement is recommended

to promote adherence, in addition to patient education and I C
involvement.

75
 Diagnosis of disease progression
The long-term clinical follow-up of CCS patients is mostly empirical and based on sound
clinical judgment.

Recommendations for diagnosis of disease progression in patients with

established CCS
Recommendations Class Level

Asymptomatic patients with established chronic coronary syndromes

Regardless of symptoms, periodic visits (e.g. annual) to a

general practitioner or cardiovascular healthcare professional
are recommended to evaluate cardiovascular risk factor control
I C
and to assess changes in risk status, disease status, and
comorbidities that may require lifestyle, medical, or procedural
interventions.

Symptomatic patients with established chronic coronary syndromes

Reassessment of CAD status is recommended in patients with

deteriorating LV systolic function that cannot be attributed to a I C
reversible cause (e.g. longstanding tachycardia or myocarditis).

Risk stratification is recommended in patients with new or

I C
worsening symptoms, preferably using stress imaging.

In patients with symptoms refractory to medical treatment or at

high risk of adverse events, invasive coronary angiography
(with FFR/iFR when necessary) is recommended for risk I C
stratification and for possible revascularization aimed at
improving symptoms and prognosis.

In CCS patients with symptoms refractory to medical

treatment, and who have had previous coronary
IIa B
revascularization, CCTA should be considered to evaluate
bypass graft or stent patency (for stents ≥3 mm).
CAD, coronary artery disease; CCS, chronic coronary syndrome; CCTA, coronary computed tomography
angiography; FFR, fractional flow reserve; iFR, instantaneous wave-free ratio; LV, left ventricular.

76
Figure 18 Follow-up of patients with established CCS

ACS, acute coronary syndrome; AF, atrial fibrillation; CABG, coronary aortic
bypass grafting; CAD, coronary artery disease; CCS, chronic coronary
syndrome; CKD, chronic kidney disease; ECG, electrocardiogram; LV, left
ventricle; PAD, peripheral artery disease; PCI, percutaneous coronary
intervention; RV, right ventricle.

77
Treatment of myocardial revascularization failure
One in five revascularized patients needs a repeat revascularization within
the first 5 years, with higher risk after PCI as compared to CABG.

Recommendations for treatment of revascularization failure

Recommendations Class Level

DES is recommended over drug-coated balloons for

I A
treatment of in-DES restenosis.

LIMA is indicated as the conduit of choice for redo CABG in

I B
patients in whom the LIMA was not used previously.

Redo CABG should be considered for patients without a

IIa B
patent LIMA graft to the LAD.

PCI of the bypassed native artery should be considered

IIa B
over PCI of the bypass graft.
CABG, coronary artery bypass grafting; DES, drug-eluting stent; LAD, left
anterior descending; LIMA, left internal thoracic artery; PCI, percutaneous
coronary intervention.

78
Recurrent or refractory angina/ischaemia

Despite the use of antianginal drugs and/or PCI or CABG, the proportion of
patients with CCS who have daily or weekly angina ranges from 2% to 24%.

Recommendations for recurrent or refractory angina/ischaemia

Recommendations Class Level

In patients with refractory angina leading to poor quality of

life and with documented or suspected ANOCA/INOCA,
invasive coronary functional testing is recommended to I B
define ANOCA/INOCA endotypes and appropriate
treatment, considering patient choices and preferences.

In patients with debilitating angina and

obstructive CAD refractory to optimal medical and
revascularization strategies, a reducer device for coronary IIb B
sinus constriction may be considered to improve symptoms,
in experienced centres.
ANOCA, angina with non-obstructive coronary arteries; CAD, coronary artery
disease; INOCA, ischaemia with non-obstructive coronary arteries.

79
Contents
Essential Messages ................................................................................................................................. 1
Authors and legal information ............................................................................................................ 1
Key messages ...................................................................................................................................... 2
Gaps in evidence ................................................................................................................................. 3
Authors and publication ......................................................................................................................... 5
Preamble ................................................................................................................................................. 6
Introduction ............................................................................................................................................ 7
Pathophysiology and clinical consequences of elevated BP and hypertension ..................................... 8
Measuring blood pressure .................................................................................................................... 10
Introduction and pertinent definitions ............................................................................................. 10
Practical recommendations for measuring BP ................................................................................. 11
Clinical validation of equipment for measuring BP....................................................................... 11
Office BP measurement ................................................................................................................ 11
Home BP measurement ................................................................................................................ 13
Ambulatory BP measurement....................................................................................................... 14
Comparison of home and ambulatory BP monitoring .................................................................. 15
Definition and classification of elevated BP and hypertension and CVD risk assessment ................... 18
Definition and classification of elevated BP and hypertension ........................................................ 18
Predicting cardiovascular disease risk .............................................................................................. 19
Refining cardiovascular disease risk estimation beyond risk models ............................................... 21
Summary of the CVD risk stratification approach for allocating BP treatment ................................ 22
Diagnosing hypertension and investigating underlying causes ............................................................ 24
Screening for hypertension ............................................................................................................... 24
Confirming the diagnosis of hypertension ........................................................................................ 25
Baseline assessment and diagnostic approach ................................................................................. 26
Drug adherence and persistence with treatment ........................................................................ 26
Routine and optional tests ............................................................................................................ 28
The kidney ..................................................................................................................................... 31
The heart ....................................................................................................................................... 32
The arteries ................................................................................................................................... 33
Genetic testing .............................................................................................................................. 33
Resistant hypertension: definition and diagnosis ............................................................................. 34
Secondary hypertension when to screen further investigations ...................................................... 35
Preventing and treating elevated blood pressure and hypertension ................................................... 40
Overview ........................................................................................................................................... 40
 Prevention strategies in early life ..................................................................................................... 40
Non pharmacological interventions.................................................................................................. 40
Pharmacological interventions ......................................................................................................... 44
Selecting patients for pharmacological blood pressure lowering treatment ................................... 49
Intensity of BP lowering therapy and ideal treatment targets ......................................................... 51
The ideal target of BP lowering treatment ................................................................................... 51
Duration and monitoring of drug therapy .................................................................................... 53
Device based blood pressure lowering ............................................................................................. 54
Managing specific patient groups or circumstances ............................................................................ 55
Young adulthood 18-40 years ........................................................................................................... 55
Pregnancy.......................................................................................................................................... 56
Definition and epidemiology......................................................................................................... 56
Risk of recurrence of hypertensive disorders in a subsequent pregnancy ................................... 56
Maintaining BP lowering in very old or frail patients ....................................................................... 58
Orthostatic hypotension with supine hypertension ......................................................................... 59
Diabetes ............................................................................................................................................ 59
Chronic kidney disease...................................................................................................................... 60
Cardiac disease.................................................................................................................................. 61
Chronic cerebrovascular disease and or cognitive impairment ....................................................... 62
Different ethnic groups ..................................................................................................................... 62
Resistant hypertension ..................................................................................................................... 63
Management of specific causes of secondary hypertension - renovascular hypertension.............. 64
Acute and short term lowering of BP ................................................................................................... 65
Acute BP management in acute ischaemic stroke ............................................................................ 65
Acute BP management in pre eclampsia and severe hypertension in pregnancy ........................... 66
Patient centred care in hypertension ................................................................................................... 67
Overview ........................................................................................................................................... 67
Self measuring and monitoring ......................................................................................................... 68
Facilitating medication adherence and persistence ......................................................................... 69
Multidisciplinary management ......................................................................................................... 70
Essential Messages

Authors and legal information

2024 ESC Guidelines for the management of elevated blood pressure and hypertension
Developed by the task force on the management of elevated blood pressure and
hypertension of the European Society of Cardiology (ESC)
Endorsed by the the European Society of Endocrinology (ESE) and the European Stroke
Organisation (ESO)
Chairpersons
John William McEvoy
Department of Cardiology,
University of Galway School of
Medicine, and
National Institute for Prevention
and Cardiovascular Health,
Galway, Ireland
Rhian M. Touyz
Department of Medicine, McGill University,
Department of Family Medicine, McGill University,
Montreal, Canada, and the Research Institute of
the McGill University Health Centre, McGill
University, Montreal, Canada
Task Force Members:
Cian P. McCarthy (Task Force Co-ordinator) (United States), Rosa Maria Bruno (Task Force
Co-ordinator) (France), Sofie Brouwers (Belgium), Michelle D. Canavan, (Ireland), Claudio
Ceconi (Italy), Ruxandra Maria Christodorescu (Romania), Stella S. Daskalopoulou (Canada),
Charles J. Ferro1 (United Kingdom), Eva Gerdts (Norway), Henner Hanssen (Switzerland),
Julie Harris (United Kingdom), Lucas Lauder (Switzerland/Germany), Richard J. McManus
(United Kingdom), Gerard J. Molloy (Ireland), Kazem Rahimi (United Kingdom), Vera Regitz-
Zagrosek (Germany), Gian Paolo Rossi2 (Italy), Else Charlotte Sandset3 (Norway), Bart
Scheenaerts (Belgium), Jan A. Staessen (Belgium), Izabella Uchmanowicz (Poland), Maurizio
Volterrani (Italy).
1
Representing the European Renal Association (ERA).
2
Representing the European Society of Endocrinology (ESE).
3
Representing the European Stroke Organisation (ESO).
ESC subspeciality communities having participated in the development of this document:
Associations: Association of Cardiovascular Nursing & Allied Professions (ACNAP),
European Association of Preventive Cardiology (EAPC), European Association of
Percutaneous Cardiovascular Interventions (EAPCI), Heart Failure Association (HFA).
Councils: Council for Cardiology Practice, Council on Hypertension, Council on Stroke.
Working Groups: Aorta and Peripheral Vascular Diseases, Cardiovascular Pharmacotherapy,
E-Cardiology.
Patient forum

Adapted from the 2024 ESC Guidelines for the management of elevated blood pressure and
hypertension European Heart Journal; 2024 – doi:10.1093/eurheartj/ehae178

1
Key messages

(1) Given the demographic transition and the worldwide ageing of

populations, the number of individuals with elevated BP or hypertension
is increasing worldwide.
(2) The trajectory of BP control appears to be worsening in North
America, in some (but not all) European countries, and elsewhere around
the world.
(3) The risk for CVD attributable to BP is on a continuous log-linear
exposure variable scale, not a binary scale of normotension vs.
hypertension.
(4) Blood pressure-lowering drugs can reduce CVD risk even among
individuals not traditionally classified as hypertensive. Accordingly, a
new BP category called ‘elevated BP’ is introduced. Elevated BP is
defined as an office systolic BP of 120–139 mmHg or diastolic BP of
70–89 mmHg. Hypertension remains defined as office BP of ≥140/90
mmHg.
(5) Hypertension in women is under-studied in basic, clinical, and
population research.
(6) Hypertension-mediated organ damage suggests long-standing or
severe hypertension and is associated with increased CVD risk.
(7) Absolute CVD risk must be considered when assessing and
managing elevated BP.
(8) Despite the growing number of hypertension guidelines, the rates of
diagnosis, treatment, and control of hypertension (and elevated BP)
remain suboptimal. A major factor underlying this is poor
implementation of evidence-based guidelines in real-world clinical
practice.
(9) One of the most important changes in the 2024 Guidelines is the
focus on evidence related to CVD outcomes of BP-lowering interventions
rather than BP lowering alone.
(10) Irrespective of the threshold BP above which BP-lowering treatment
(lifestyle or pharmacological or other treatment) is recommended, the
on-treatment BP target is 120–129/70–79 mmHg for all adults, provided
this treatment is well tolerated. There are several important exceptions
to these targets and individualized decision-making is always the most
important priority.

2
Gaps in evidence

(1) Drivers of worsening trajectories of BP control in women and men.

(2) Need for sex-specific data on epidemiology, risk factors, and
pathophysiology of hypertension. Need for more prospective studies to
assess women’s and men’s specific CVD risk factors pertinent to adults
with elevated BP and hypertension, due to biological and socio-cultural
conditions. This includes sex-specific weighting of traditional risk
factors, as well as inclusion of sex-dependent, non-traditional, vascular
risk factors such as stress, socio-economic conditions, and others. We
are also lacking data on sex-specific hormonal and genetic mechanisms
and pathophysiology in the human. Another important area in need of
investigation is a better understanding of the role of gender in the
management of elevated BP and hypertension (including gender-driven
barriers in accessing medical care and adherence).
(3) More widespread validation of home BP measuring devices.
Validation protocols for cuffless BP measurement devices have just
recently been proposed and need to be tested.
(4) Clinical effectiveness of HMOD in directing intensity of care and
personalized approaches in managing elevated BP and hypertension.
(5) Best practice to screen and manage primary aldosteronism.
(6) Clinical benefits of treating low CVD-risk individuals with
elevated BP and further data strengthening the use of BP-lowering
medication among high-risk persons with baseline systolic BP of 120–
129 mmHg.
(7) Need for more data on the sex-specific optimal dosing, effects, and
adverse effects of BP-lowering drugs,1020 in particular from specifically
planned prospective randomized trials.
(8) More consideration for overall CVD outcomes of BP-lowering
interventions.
(9) More European data (RCTs, real life) about the beneficial effect of
treating patients with elevated BP and hypertension with polypills
(inclusive of non-BP lowering medications).
(10) Cardiovascular disease outcomes-based data on MRAs as add-on
therapy solely for resistant hypertension.
(11) Trials on the BP-lowering effects of newer antidiabetic drugs (such
as SGLT2 inhibitors and GLP-1 receptor agonists) or drugs that now
have indications for other conditions, such as finerenone or sacubitril-
valsartan.

3
(12) Beneficial BP and CVD effects of increasing dietary potassium
intake and other lifestyle interventions. Studies to disentangle the effect
of sodium reduction vs. the effect of potassium supplementation
on BP control and CVD outcomes.
(13) RCTs comparing single-pill combination therapy with fixed doses
vs. multiple monotherapies and their effects on CVD outcomes.
(14) Cardiovascular outcomes trials of renal denervation.
(15) BP-lowering treatment RCTs on different ethnic and migrant groups
established in Europe.
(16) Pharmacological BP management in young adults (aged <40 years)
and better data on the efficacy of a life-course approach for the drug
management of BP.
(17) Cardiovascular disease outcomes in moderately to severely frail
and/or very elderly persons where BP medications have been
deprescribed, and the impact of competing risks.
(18) Management of renal artery disease with haemodynamically stable
but severe stenosis (i.e. without high-risk features).
(19) Need for clinical trials on managing hypertension in patients treated
with anticancer drugs or anti-rejection drugs in recipients of an allograft
transplant.
(20) Hypertension management in the setting of climate changes, global
warming, air and other forms of pollution, pandemics, war zones, and in
the context of drug restrictions experienced in some low-to-middle-
income countries.
(21) Need to improve implementation of guidelines by healthcare
providers.
(22) How to develop sustainable hypertension care at the intersection of
growing numbers of patients and limited resources.
(23) Treat-to-target trials specifically testing BP-lowering drugs among
drug-naïve persons with baseline BP of 120–129 mmHg and
increased CVD risk.

4
Authors and publication
2024 ESC Guidelines for the management of elevated blood pressure and hypertension*
Developed by the task force on the management of elevated blood pressure and
hypertension of the European Society of Cardiology (ESC).
Endorsed by the the European Society of Endocrinology (ESE) and the European Stroke
Organisation (ESO).
Chairpersons
John William McEvoy
Department of Cardiology, University of
Galway School of Medicine, and
National Institute for Prevention and
Cardiovascular Health, Galway, Ireland
Rhian M. Touyz
Department of Medicine, McGill University,
Department of Family Medicine,
McGill University, Montreal, Canada, and
the Research Institute of the McGill University
Health Centre, McGill University, Montreal,
Canada
Task Force Members:
Cian P. McCarthy (Task Force Co-ordinator) (United States), Rosa Maria Bruno (Task Force
Co- ordinator) (France), Sofie Brouwers (Belgium), Michelle D. Canavan, (Ireland), Claudio
Ceconi (Italy), Ruxandra Maria Christodorescu (Romania), Stella S. Daskalopoulou (Canada),
Charles J. Ferro1 (United Kingdom), Eva Gerdts (Norway), Henner Hanssen (Switzerland),
Julie Harris (United Kingdom), Lucas Lauder (Switzerland/Germany), Richard J. McManus
(United Kingdom), Gerard J. Molloy (Ireland), Kazem Rahimi (United Kingdom), Vera Regitz-
Zagrosek (Germany), Gian Paolo Rossi2 (Italy), Else Charlotte Sandset3 (Norway), Bart
Scheenaerts (Belgium), Jan A. Staessen (Belgium), Izabella Uchmanowicz (Poland), Maurizio
Volterrani (Italy).
1
Representing the European Renal Association (ERA).
2
Representing the European Society of Endocrinology (ESE).
3
Representing the European Stroke Organisation (ESO).
ESC subspecialty communities having participated in the development of this document:
Associations: Association of Cardiovascular Nursing & Allied Professions (ACNAP),
European Association of Preventive Cardiology (EAPC), European Association of
Percutaneous Cardiovascular Interventions (EAPCI), Heart Failure Association (HFA).
Councils: Council for Cardiology Practice, Council on Hypertension, Council on Stroke.
Working Groups: Aorta and Peripheral Vascular Diseases, Cardiovascular Pharmacotherapy,
E-Cardiology.
Patient forum
*
Adapted from the 2024 ESC Guidelines for the management of elevated blood pressure and
hypertension (European Heart Journal; 2024 – doi:10.1093/eurheartj/ehae178) based on
uncorrected proofs.

5
Preamble
ESC Classes of recommendations and levels of evidence

Table 1 Classes of recommendations

Definition Wording to use

Class Evidence and/or general agreement that a Is recommended

I given treatment or procedure is beneficial, or is indicated
useful, effective.

Class Conflicting evidence and/or a divergence of opinion about the

II usefulness/efficacy of the given treatment or procedure.

Class Weight of evidence/opinion is in favour Should be

IIa of usefulness/efficacy. considered

Class Usefulness/efficacy is less well May be

IIb established by evidence/opinion. considered

Class Evidence or general agreement that the Is not

III given treatment or procedure is not useful/ recommended
effective, and in some cases may be
harmful.

Table 2 Levels of evidence

Level of Data derived from multiple randomized clinical trials or

evidence A meta-analyses.

Level of Data derived from a single randomized clinical trial or

evidence B large non-randomized studies.

Level of Consensus of opinion of the experts and/or small

evidence C studies, retrospective studies, registries.

6
Introduction
The European Society of Cardiology (ESC) has recently completed a
comprehensive review of the existing state of medical evidence and
clinical trial data relating to the management of elevated blood pressure
and hypertension. Classes of recommendations and levels of evidence
have been evaluated and scored according to the definitions shown
in Table 1 and Table 2.
This quick reference booklet summarizes clinical care information
extracted from the full guidelines. For greater details, please refer to the
published full guideline available at www.escardio.org/guidelines.
While the current document builds on prior guidelines, it also
incorporates important updates and new recommendations based on
current evidence. For example:
1. The title has changed to ‘Guidelines on the management
of elevated blood pressure and hypertension’. This is
based on evidence that the risk for cardiovascular
disease (CVD) attributable to blood pressure (BP) is on a
continuous exposure scale, not a binary scale of
normotension vs. hypertension.
2. A new BP category called ‘Elevated BP’ is introduced.
Elevated BP is defined as an office systolic BP of 120–
139 mmHg or diastolic BP of 70–89 mmHg.
3. A major recommendation to pursue a target
systolic BP of 120–129 mmHg among adults
receiving BP-lowering medications is introduced.
4. The current Guidelines require that, for a Class I
recommendation to be made for a drug or procedural
intervention, the evidence must show benefit
on CVD outcomes and not only BP lowering.
5. The present Guidelines consider sex and gender as an
integral component throughout the document, rather
than in a separate section at the end.
6. The Guidelines are written to make them more ‘user
friendly’, especially for general practitioners (GPs), who
provided valuable input.

7
Pathophysiology and clinical consequences of
elevated BP and hypertension
The pathophysiology of hypertension involves complex interactions between
environmental and behavioural factors, genes, hormonal networks, and
multiple organ systems (renal, cardiovascular, and central nervous system)
(Figure 1).
In addition, vascular and immune mechanisms are involved. Dysregulation of
these processes leads to hypertension, which if uncontrolled, can lead to
hypertension- mediated organ damage (HMOD).
Figure 1 Pathophysiology of elevated BP and hypertension.

BP, blood pressure; PNS, parasympathetic nervous system; RAAS, renin–angiotensin-aldosterone

system; SNP, single-nucleotide polymorphism; SNS, sympathetic nervous system.

8
Longstanding hypertension causes organ damage and ultimately leads
to cardiovascular, cerebrovascular, and clinical renal disease, which are
all major contributors to the global burden of chronic disease (Figure 2).
We use the term ‘hypertension-mediated organ damage’ to indicate the
presence of subclinical complications of hypertension that indicate high
risk for subsequent clinical events. HMOD may have different profiles in
men and women; for instance, left ventricular hypertrophy (LVH) and left
atrial dilatation are more frequent in women.
Figure 2 Persistently elevated BP and hypertension lead to
hypertensionmediated organ damage and CVD.

CAD, coronary artery disease; GFR, glomerular filtration rate; LA, left
atrial; LV, left ventricular, LVH, left ventricular hypertrophy.

9
Measuring blood pressure

Introduction and pertinent definitions

The current Guidelines promote use of out-of-office measurement for
diagnosis and ongoing management of hypertension, reflecting
increasing evidence for the stronger relationship of home and
ambulatory monitoring with outcomes, the ability to detect white coat
and masked hypertension, new BP thresholds (Table 3), and evidence
supporting patient involvement and shared decision-making.

Table 3 Comparison of office, home, and

ambulatory BP measurement thresholds for elevated BP and
hypertension

ABPM, ambulatory blood pressure monitoring; BP, blood pressure.

a
The BP thresholds provided assume that a standardized approach to
office BP measurement is performed (Figure 3). However, evidence
indicates that office BP measurement in routine clinical settings is often
not done using a standardized approach and, in this case, the routine
office BP value may be 5–10 mmHg higher than it would have been if
measured using the recommended standardized approach.

10
Practical recommendations for measuring BP

Clinical validation of equipment for measuring BP

BP measurement must be undertaken using a device that has been
clinically validated and confirmed accurate. Of the commercially
available oscillometric BP measurement devices, as few as 6% have
been adequately tested. National and international organizations provide
lists of validated monitors (e.g. www.stridebp.org, www.validatebp.org).

Office BP measurement
Since BP measurements are influenced by circumstances of
measurement, we recommend following a standardized method
for BP measurements in the office Figure 3.

11
Figure 3 Summary of office BP measurement.

BP, blood pressure.

12
Home BP measurement
A standardised approach to HBPM should be also used (Figure 4) when
the patient measures their own BP at home using a validated monitor
(usually an upper-arm oscillometric cuff device).
Figure 4 Summary of home BP measurement.

BP, blood pressure; HBPM, home blood pressure measurement.

Morning HBPM readings should be obtained before breakfast and before intake of
a

medication but not immediately after awakening.

13
Ambulatory BP measurement
Ambulatory BP measurement (summarized in Figure 5) is an out-of-
office BP measurement that uses a fully automated device, usually for a
24-hour period.
Figure 5 Summary of ambulatory BP measurement.

ABPM, ambulatory blood pressure measurement; BP, blood pressure.

14
Comparison of home and ambulatory BP monitoring

Home and ambulatory monitoring are both able to differentiate between

hypertensive phenotypes such as white coat and masked hypertension.
However, around 15% of people will have diagnostic disagreement, often
clinically relevant. The advantages and disadvantages of home and
ambulatory monitoring are outlined in Table 4.

Table 4 Comparison of ambulatory and home BP monitoring

Ambulatory monitoring

Advantages
Can identify white coat and masked hypertension
Measurement in real-life settings and during usual activities
Stronger prognostic evidence
Night-time readings
Abundant information from a single investigation, including short-term
diurnal BP variability
Additional BP phenotyping (e.g. nocturnal dipping status)
Disadvantages
Relatively expensive and sometimes limited availability
Can be uncomfortable and affect sleep

Home monitoring

Advantages
Identify white coat and masked hypertension
Cheap and widely available
Measurement at home, which may be more relaxed than doctor’s office
Patient engagement in BP measurement and telemedicine potential
Easily repeated and used over longer periods to assess day-to-
day BP variability
Disadvantages
Only static BP at rest is typically available
Potential for measurement error due to improper measurement
technique or unvalidated or poorly calibrated device
Nocturnal readings not usually possible
BP, blood pressure.

15
Recommendations for measuring BP

Recommendations Class Level

All adult patients (≥18 years) are recommended to have

their office and/or out-of-office BP measured on an
I C
opportunistic basis and recorded in their medical file, and
be told what their current BP is.

Out-of-office BP measurement is recommended for

diagnostic purposes, particularly because it can detect
both white coat hypertension and masked hypertension.
Where out-of-office measurements are not logistically
I B
and/or economically feasible, then it is recommended that
the diagnosis be confirmed with a repeat
office BP measurement using the correct standardized
measurement technique.

It is recommended that office BP should be measured in

both arms at least at the first visit, because a between-
arm systolic BP difference of >10 mmHg is associated I B
with an increased CVD risk and may indicate arterial
stenosis.

If a between-arm difference of >10 mmHg in

systolic BP is recorded, then it is recommended that all
I B
subsequent BP readings use the arm with the
higher BP reading.

Out-of-office BP measurement is recommended for

ongoing management to quantify the effects of treatment
and guide BP- lowering medication titration, and/or
identify possible causes of side effects (e.g. symptomatic
hypotension). Where out-of-office measurements are not I B
logistically and/or economically feasible, then ongoing
management is recommended to be based on repeated
office BP measurements using the correct standardized
measurement technique.

It is recommended that all patients

undergoing BP measurement also undergo pulse
I C
palpation at rest to determine heart rate and arrhythmias
such as atrial fibrillation.

16
 Most automated oscillometric monitors have not been
validated for BP measurement in atrial
fibrillation; BP measurement should be considered using IIa C
a manual auscultatory method in these circumstances
where possible.

An assessment for orthostatic hypotension (≥20

systolic BP and/or ≥10 diastolic BP mmHg drop at 1 and/
or 3 minutes after standing) should be considered at least
at the initial diagnosis of elevated BP or hypertension and IIa C
thereafter if suggestive symptoms arise. This should be
performed after the patient is first lying or sitting for 5
minutes.

Other BP measures and indices (pulse

pressure, BP variability, exercise BP) may be considered
IIb C
to provide additional clinical information on CVD risk in
some circumstances.
BP, blood pressure; CVD, cardiovascular disease.

17
Definition and classification of elevated BP and
hypertension and CVD risk assessment

Definition and classification of elevated BP and hypertension

To aid pharmacologic treatment decisions, the 2024 ESC Guidelines

recommend a simplified categorization of adults according to
their BP (Figure 6). However, it is important to stress that the risk
of CVD attributable to BP is continuous.
Figure 6 Blood pressure categories.

18
ABPM, ambulatory blood pressure monitoring, BP, blood pressure; DBP, diastolic
blood pressure; HBPM, home blood pressure monitoring; SBP, systolic blood
pressure. Normotensive 24 h or night-time ABPM are considered equivalent to
daytime ABPM and we also note that the respective non-daytime ABPM thresholds
for elevated BP and hypertension diagnosis are listed in Table 3.

Predicting cardiovascular disease risk

Certain conditions on their own are associated with CVD risk such that
patients with elevated BP alongside these conditions can be considered
for BP-lowering therapy (Figure 7).
Figure 7 Sufficiently high cardiovascular risk conditions that
warrant BP-lowering treatment among adults with elevated BP.

CKD, chronic kidney disease; eGFR, estimated glomerular filtration rate.

a
coronary heart disease, cerebrovascular disease, peripheral arterial
disease.
b
see Figure 12.
c
SCORE2-Diabetes should be considered to identify lower risk individuals
(<10% 10-year CVD risk), who may not require BP-lowering medication,
particularly in individuals <60 years.

19
In the absence of these sufficiently high-risk conditions, risk-prediction
models (SCORE2 and SCORE-OP) have been developed in the general
population to predict 10-year risk of CVD.

Recommendations for assessing CVD risk among individuals with

elevated BP (office systolic BP 120–139 mmHg or diastolic BP 70–
89 mmHg)
Recommendations Class Level

It is recommended to use a risk-based approach in the

treatment of elevated BP, and individuals with moderate or
severe CKD, established CVD, HMOD, diabetes mellitus, or I B
familial hypercholesterolaemia are considered at increased
risk for CVD events.
SCORE2 is recommended for assessing 10-year risk of fatal
and non-fatal CVD among individuals aged 40–69 years with
elevated BP who are not already considered at increased risk I B
due to moderate or severe CKD, established CVD, HMOD,
diabetes mellitus, or familial hypercholesterolaemia.
SCORE2-OP is recommended for assessing the 10-year risk
of fatal and non-fatal CVD among individuals aged ≥70
years with elevated BP who are not already considered at
I B
increased risk due to moderate or severe CKD,
established CVD, HMOD, diabetes mellitus, or familial
hypercholesterolaemia.
It is recommended that, irrespective of age, individuals with
elevated BP and a SCORE2 or SCORE2-OP CVD risk of
I B
≥10% be considered at increased risk for CVD for the
purposes of risk-based management of their elevated BP.
SCORE2-Diabetes should be considered to
estimate CVD risk among type 2 diabetes mellitus patients IIa B
with elevated BP, particularly if they are <60 years of age.
BP, blood pressure; CKD, chronic kidney disease; CVD, cardiovascular
disease; HMOD, hypertension-mediated target organ damage; SCORE2,
Systematic COronary Risk Evaluation 2; SCORE2-OP, Systematic
COronary Risk Evaluation 2–Older Persons. Established CVD: coronary
artery disease, cerebrovascular disease, peripheral arterial disease, or
heart failure.
For details on HMOD see Section 7 of the full guidelines.

20
Refining cardiovascular disease risk estimation
beyond risk models
The SCORE2 and SCORE2-OP risk-prediction models incorporate
traditional risk factors such as age, sex, SBP cholesterol values, and
smoking status to predict 10- year risk of CVD. Risk modifiers, which
mean non-traditional CVD risk factors that improve the predictive
performance (i.e. discrimination) of CVD risk-prediction models, are
listed in Figure 8.
Figure 8 Cardiovascular disease risk factors to consider for
up-classification of risk.

ASCVD, atherosclerotic cardiovascular disease; COVID-19, Coronavirus disease 2019; HIV,

human immunodeficiency virus.

21
 Recommendation for refining cardiovascular disease risk

Recommendation Class Level

After assessing 10-year predicted CVD risk and non-

traditional CVD risk factors, if a risk-based BP-lowering
treatment decision remains uncertain for individuals with
elevated BP, measuring CAC score, carotid or femoral
plaque using ultrasound, high-sensitivity cardiac
troponin or B-type natriuretic peptide biomarkers, or IIb B
arterial stiffness using pulse wave velocity, may be
considered to improve risk stratification among patients
with borderline increased 10-year CVD risk (5% to
<10% risk) after shared decision-making and considering
costs.
BP, blood pressure; CAC, coronary artery calcium; CVD, cardiovascular
disease; HIV, human immunodeficiency virus.

Summary of the CVD risk stratification approach

for allocating BP treatment
In persons with elevated BP, combined with 10-year CVD risk-prediction
models, sufficiently high cardiovascular risk conditions, risk modifiers,
and risk tools (like biomarkers or imaging tests) should be used for
stratifying risk when allocating BP-lowering treatment (Figure 9).
All patients with confirmed hypertension are recommended to
receive BP-lowering treatment and no further risk stratification is
needed.

Figure 9 Summary of CVD risk-stratification approach

for BP treatment in adults with elevated BP.

22
23
ASCVD, atherosclerotic cardiovascular disease; BP, blood pressure; CAC,
coronary artery calcium; CKD, chronic kidney disease; CVD,
cardiovascular disease; DBP, diastolic blood pressure; DM, diabetes
mellitus; FH, familial hypercholesterolaemia; HMOD, hypertension-
mediated target organ damage; NT-proBNP, N-terminal pro-brain
natriuretic peptide; SBP, systolic blood pressure; SCORE2, Systematic
COronary Risk Evaluation; SCORE2-OP, Systematic COronary Risk
Evaluation–Older Persons.

Diagnosing hypertension and investigating

underlying causes

Screening for hypertension

Recommendations for BP screening

Recommendations Class Level

Opportunistic screening for elevated BP and

hypertension should be considered at least every 3 years IIa C
for adults aged <40 years.

Opportunistic screening for elevated BP and

hypertension should be considered at least annually for IIa C
adults aged ≥40 years.

In individuals with elevated BP who do not currently

meet risk thresholds for BP-lowering treatment, a
IIa C
repeat BP measurement and risk assessment within 1
year should be considered.

Other forms of screening for hypertension (i.e. systematic

screening, self-screening, and non-physician screening)
IIb B
may be considered, depending on their feasibility in
different countries and healthcare systems.
BP, blood pressure.

24
Confirming the diagnosis of hypertension
Assessment at a single visit by office BP has lower specificity compared
with out- of-office BP for diagnosing hypertension. Accordingly, a
protocol for confirming the diagnosis of hypertension is proposed
(Figure 10), with out-of-office BP measurement (ABPM and/or HBPM)
the preferred method for confirming cases of elevated BP or
hypertension. If these measurements are not logistically or economically
feasible, then diagnosis can be made on repeated
office BP measurements on more than one visit.
Figure 10 Protocol for confirming hypertension diagnosis.

BP, blood pressure; CVD, cardiovascular disease; SCORE2, Systematic

COronary Risk Evaluation; SCORE2-OP, Systematic COronary Risk
Evaluation–Older Persons.

25
Baseline assessment and diagnostic approach

Drug adherence and persistence with treatment

Adherence is defined as the extent to which a patient’s behaviour, for

example with respect to taking medication, coincides with agreed
recommendations from a healthcare provider. Persistence represents
the amount of time from initiation to discontinuation of therapy.
Non-adherence to BP-lowering therapy depends on many factors (Figure
11). Effective patient–physician communication is crucial to improve
adherence. Single- pill combinations improve persistence in BP-lowering
treatment and are associated with lower all-cause mortality.
Figure 11 Definitions, assessments, and potential
interventions for the three phases of adherence to BP-
lowering medications.

26
Recommendation for assessing adherence and persistence with
treatment

Recommendation Class Level

Objective evaluation of adherence (either directly

observed treatment or detecting prescribed drugs in
blood or urine samples) should be considered in the IIa B
clinical work-up of patients with apparent resistant
hypertension, if resources allow.

27
Routine and optional tests
Routine tests include laboratory and clinical tests to detect
increased CVD risk, HMOD and secondary hypertension, recommended
in the initial work-up of a patient with elevated BP or hypertension (Table 5).

Table 5 Routine tests recommended in the initial work-up of a patient

with elevated BP or hypertension

Routine test Clinical utility

Fasting blood glucose (and HbA1c if Assessing CVD risk and
fasting blood glucose is elevated) comorbidities
Serum lipids: total Assessing CVD risk
cholesterol, LDL cholesterol, HDL and
non-HDL cholesterol, triglycerides
Blood sodium and potassium, Screening secondary
haemoglobin and/or haematocrit, hypertension (primary
calcium, and TSH aldosteronism, Cushing’s
disease, polycythaemia,
hyperparathyroidism, and
hyperthyroidism)
Blood creatinine and eGFR; urinalysis Assessing CVD risk
and urinary albumin-to-creatinine ratio and HMOD Guiding
treatment choice Screening
secondary hypertension
(renoparenchymal and
renovascular)
12-lead ECG Assessing HMOD (left atrial
enlargement, left ventricular
hypertrophy)
Assessing irregular pulse
and other comorbidities
(atrial fibrillation, previous
acute myocardial infarction)
CVD, cardiovascular disease; ECG, electrocardiogram; eGFR, estimated
glomerular filtration rate; HbA1c, glycated haemoglobin; HDL, high-
density lipoprotein; HMOD, hypertension-mediated target organ damage;
LDL, lowdensity lipoprotein; TSH, thyroid-stimulating hormone.

28
Optional tests for HMOD (Table 6) are useful to identify patients with
elevated BP who deserve BP-lowering treatment; however, these tests
may also help to optimize treatment and overcoming therapeutic inertia
in patients with hypertension. In all patients, a careful medical history,
medication history, and physical examination is to be collected to
identify factors and risks potentially contributing to elevated BP and
hypertension (See Tables S2 and S3 of full guidelines).

Table 6 Optional tests that may be used as clinically indicated in the

initial work-up of a patient with elevated BP or hypertension to
assess HMOD or established CVD
Optional test Clinical utility
Echocardiography Assessing HMOD (hypertensive heart disease)
Assessing established CVD (previous acute
myocardial infarction, heart failure)
Assessing thoracic aorta dilation
CAC by cardiac CT or Assessing HMOD (atherosclerotic plaque)
carotid or femoral
artery ultrasound
imaging
Large artery stiffness Assessing HMOD (arterial stiffness)
(carotid- femoral or
brachial-ankle PWV)
Ankle–brachial index Assessing established CVD (lower-extremity
arterial disease)
Abdominal ultrasound Assessing established CVD (abdominal
aneurysm)
Fundoscopy Assessing HMOD (hypertensive retinopathy)
Diagnosing hypertensive emergency/malignant
hypertension (haemorrhages and exudates,
papilloedema)
CAC, coronary artery calcium; CT, computed tomography; CVD, cardiovascular
disease; HMOD, hypertension mediated target organ damage; PWV, pulse wave
velocity.
HMOD assessment is also an important way to identify young adults <40
years old who have increased CVD risk, since 10-year estimated CVD risk
by SCORE2 cannot be calculated in this age. More details on diagnostic
thresholds for HMOD are provided Figure 12.

29
Figure 12 Tests and criteria for defining HMOD and
considerations for their use in clinical practice.

30
ACR, albumin:creatinine ratio; BP, blood pressure; BSA, body surface
area; CT, computed tomography; CVD, cardiovascular disease; ECG,
electrocardiogram; eGFR, estimated glomerular filtration rate; HMOD,
hypertensionmediated target organ damage; hs-cTnT, high-sensivity
cardiac troponin T; LA, Left atrial; LV, left ventricular; LVH, left ventricular
hypertrophy; NT-proBNP, N-type pro-brain natriuretic protein; PWV, pulse
wave velocity; RWT, relative wall thickness; SCORE2, Systematic
COronary Risk Evaluation 2; SCORE2-OP, Systematic COronary Risk
Evaluation 2–Older Persons.

The kidney

Chronic kidney disease is defined as abnormalities of kidney structure or

function, present for at least 3 months with implications for health.
Intensive BP control in patients with CKD reduces rates
of CVD events. CKD can influence the choice of BP-lowering treatment,
as well as newer drugs for cardiovascular prevention, such as sodium–
glucose co-transporter 2 (SGLT2) inhibitors and finerenone (non-
steroidal mineralocorticoid receptor antagonist).

Recommendations for assessing renal HMOD

Recommendations Class Level

It is recommended to measure serum creatinine, eGFR,

I B
and urine ACR in all patients with hypertension.

If moderate-to-severe CKD is diagnosed, it is

recommended to repeat measurements of serum I C
creatinine, eGFR, and urine ACR at least annually.

Renal ultrasound and Doppler examination should be

considered in hypertensive patients with CKD to assess
kidney structure and determine causes of CKD and to
IIa C
exclude renoparenchymal and renovascular
hypertension. CT or magnetic resonance renal
angiography are alternative testing options.
ACR, albumin:creatinine ratio; CKD, chronic kidney disease; CT,
computed tomography; eGFR, estimated glomerular filtration rate.

31
The heart

A 12-lead ECG is a part of the initial routine work-up for all patients with
hypertension and should be repeated whenever patients present with an
irregular pulse or cardiac symptoms. The ECG should be analysed
for LVH and atrial fibrillation.
Since cardiac size and function differ by sex, sex-specific thresholds for
detecting HMOD in the heart are used to avoid under-diagnosis in
women (Figure 12).

Recommendations for assessing cardiac HMOD

Recommendations Class Level

A 12-lead ECG is recommended for all patients with

I B
hypertension.

Echocardiography is recommended in patients with

hypertension and ECG abnormalities, or signs or I B
symptoms of cardiac disease.

Echocardiography may be considered in patients with

elevated BP, particularly when it is likely to change IIb B
patient management.
BP, blood pressure; ECG, electrocardiogram.

32
The arteries

Recommendations for assessing vascular HMOD

Recommendations Class Level

Fundoscopy is recommended if BP >180/110 mmHg in the

work-up of hypertensive emergency and malignant
I C
hypertension, as well as in hypertensive patients with
diabetes.

Fundoscopy for detecting hypertensive retinopathy may be

IIb B
considered in patients with elevated BP or hypertension.

Ultrasound examination of the carotid or femoral arteries

for detecting plaque may be considered in patients with
IIb B
elevated BP or hypertension when it is likely to change
patient management.

Coronary artery calcium scoring may be considered in

patients with elevated BP or hypertension when it is likely IIb B
to change patient management.

Measurement of PWV may be considered in patients with

elevated BP or hypertension when it is likely to change IIb B
patient management.
BP, blood pressure; PWV, pulse wave velocity.

Genetic testing

Recommendations for genetic testing in hypertension management

Recommendations Class Level

Genetic testing should be considered in specialist centres for

patients suspected to have rare monogenic causes of
IIa B
secondary hypertension or for those with
phaeochromocytoma/paraganglioma.

Routine genetic testing for hypertension is not

III C
recommended.

33
Resistant hypertension: definition and diagnosis
A current definition of resistant hypertension is provided in Table 7.
Exclusion of pseudo-resistance is a prerequisite. Specifically, poor
adherence to BP-lowering treatment should be carefully verified and
white coat hypertension excluded. Objective evaluation of adherence
(either directly observed treatment or detecting prescribed drugs in
blood or urine samples) should also be considered, if resources allow.
The work-up of patients presumed to have resistant hypertension is
complex and often requires technologies that are not available to GPs.
Accordingly, we recommend these patients are referred to specialized
centres.

Recommendation for resistant hypertension work-up

Recommendation Class Level

Patients with resistant hypertension should be considered

for referral to clinical centres with expertise in IIa B
hypertension management for further testing.

34
 Table 7 Current definition of resistant hypertension
Definition of resistant hypertension
Hypertension is defined as resistant when a treatment strategy including
appropriate lifestyle measures and treatment with maximum or
maximally tolerated doses of a diuretic (thiazide or thiazide-like),
a RAS blocker, and a calcium channel blocker fail to lower office systolic
and diastolic BP values to <140 mmHg and/or <90 mmHg, respectively.
These uncontrolled BP values must be confirmed by out-of-
office BP measurements (HBPM or ABPM – Section 3.1 of pocket
guidelines or Section 5.1 of full guidelines for relevant BP thresholds).
Key considerations
Resistant hypertension is not a disease, but an indicator that should be
used to identify patients at high risk for CVD, in which secondary
hypertension is also frequent.
Pseudo-resistant hypertension must be excluded, including that caused
by non- adherence to treatment.
In patients with decreased eGFR (i.e. <30 mL/min/1.73 m2) an
adequately up-titrated loop diuretic is necessary to define resistant
hypertension.
Patients with suspected resistant hypertension should be referred to
specialized centres.
These ESC Guidelines do not include the terms ‘controlled resistant
hypertension’ (BP at target but requiring ≥4 medications) or
‘refractory hypertension’ (BP not at target despite ≥5 medications).
ABPM, ambulatory blood pressure monitoring; BP, blood pressure; CVD,
cardiovascular disease; eGFR, estimated glomerular filtration rate; HBPM, home
blood pressure monitoring; RAS, renin–angiotensin system.

Secondary hypertension when to screen further

investigations
Secondary hypertension is more prevalent than previously thought.
Depending on the definition used and the cohort studied, the prevalence
of secondary hypertension is 10–35% in all hypertensive patients and up
to 50% of patients with resistant hypertension. The most common
causes of secondary hypertension are primary aldosteronism (Figure 13)
renovascular hypertension (Figure 14) and obstructive sleep apnoea
syndrome (Figure 15).

35
Furthermore, phaeochromocytomas/paragangliomas (PPGLs) are a rare
form of secondary hypertension characterized by a highly heterogenous
clinical presentation. Optional tests that should be used to screen for
secondary hypertension are summarized in Table 8.

Table 8 Optional tests that should be used to screen for secondary

hypertension in the presence of suggestive signs, symptoms, or
medical history

Cause of secondary
Screening test
hypertension
Primary aldosteronism Aldosterone-to-renin ratio
Helpful information can also be provided by
reviewing prior potassium levels
(hypokalaemia increases the likelihood of
coexistent primary hyperaldosteronism)
Renovascular Renal Doppler ultrasound
hypertension Abdominal CT angiogram or MRI
Phaeochromocytoma/ 24 h urinary and/or plasma metanephrine
paraganglioma and normetanephrine
Obstructive sleep apnoea Overnight ambulatory polygraphy
syndrome
Renal parenchymal Plasma creatinine, sodium, and
disease potassium eGFR
Urine dipstick for blood and protein Urinary
albumin-to-creatinine ratio Renal ultrasound
Cushing’s syndrome 24 h urinary free cortisol
Low-dose dexamethasone suppression test
Thyroid disease (hyper- TSH
or hypothyroidism)
Hyperparathyroidism Parathyroid hormone
Calcium and phosphate
Coarctation of the aorta Echocardiogram
Aortic CT angiogram
CT, computed tomography; eGFR, estimated glomerular filtration rate;
MRI, magnetic resonance imaging; TSH, thyroid-stimulating hormone.

36
 Recommendations for screening for secondary hypertension

Recommendations Class Level

It is recommended that patients with hypertension

presenting with suggestive signs, symptoms or medical
I B
history of secondary hypertension are appropriately
screened for secondary hypertension.

Screening for primary aldosteronism by renin and

aldosterone measurements should be considered in all IIa B
adults with confirmed hypertension (BP ≥140/90 mmHg).
BP, blood pressure.
Figure 13 Summary of primary aldosteronism as a common
form of secondary hypertension.

HMOD, hypertension-mediated organ damage.

37
Figure 14 Summary of renovascular disease as a common
form of secondary hypertension.

CT-angio, computed tomography angiography; CV, cardiovascular; FMD,

fibromuscular dysplasia; GFR, glomerular filtration rate; MRI, magnetic
resonance imaging; RAS, renin–angiotensin system.

38
Figure 15 Summary of obstructive sleep apnoea as a common
form of secondary hypertension.

ABPM, ambulatory blood pressure monitor; CPAP, continuous positive

airway pressure.

39
Preventing and treating elevated blood
pressure and hypertension

Overview

The ultimate goal of preventing and treating elevated BP and

hypertension is to reduce CVD, to improve quality of life, and to prevent
premature death. Crucially, besides BP, other CVD risk factors need to be
comprehensively addressed (e.g. smoking, glucose, dyslipidaemia) as
detailed in the 2021 ESC Guidelines on CVD prevention in clinical
practice.

Prevention strategies in early life

Recommendation for screening for hypertension in children and

adolescents

Recommendation Class Level

Opportunistic screening with office BP measurements to

monitor development of BP during late childhood and
adolescence, especially if one or both parents have
IIa B
hypertension, should be considered to better predict
development of adult hypertension and
associated CVD risk.
BP, blood pressure; CVD, cardiovascular disease.

Non pharmacological interventions

A major underlying contributor to elevated BP and hypertension in the
general adult population is unhealthy lifestyle, with severe consequences
for all-cause and CVD mortality. As such, we give lifestyle interventions
to reduce BP and CV risk a special status in our recommendations
throughout these Guidelines (Figure 16 and Figure 17).

40
Figure 16 Physical activity according to different types of
exercise and reduction of blood pressure and overall CVD risk.

Priority is given to aerobic exercise training (green).

BP, blood pressure; CVD, cardiovascular disease.

41
Figure 17 Effects of main lifestyle factors on blood pressure
and cardiovascular risk reduction.

BP, blood pressure; CV, cardiovascular. Smoking cessation reduces

overall cardiovascular risk but not BP (long arrow). Salt reduction
reduces BP and (for persons with high baseline intake) reduces
cardiovascular risk. Increased potassium intake and higher physical
activity, as well as optimized weight management, reduce BP and are
associated with lower overall cardivascular risk (short arrows).

42
Recommendations for non-pharmacological treatment of blood
pressure and cardiovascular risk reduction
Recommendations Class Level

Restriction of sodium to approximately 2 g per day is

recommended where possible in all adults with
elevated BP and hypertension [this is equivalent to about 5 g I A
of salt (sodium chloride) per day or about a teaspoon or
less].
Moderate intensity aerobic exercise of ≥150 min/week (≥30
min, 5–7 days/week) or alternatively 75 min of vigorous
intensity aerobic exercise per week over 3 days are
I A
recommended and should be complemented with low- or
moderate-intensity dynamic or isometric resistance training
(2–3 times/week) to reduce BP and CVD risk.
It is recommended to aim for a stable and healthy BMI (e.g.
20–25 kg/m2) and waist circumference values (e.g. <94 cm in I A
men and <80 cm in women) to reduce BP and CVD risk.
Adopting a healthy and balanced diet, such as the
Mediterranean or DASH diets, are recommended to help I A
reduce BP and CVD risk.
Men and women are recommended to drink less alcohol
than the upper limit, which is about 100 g/week of pure
alcohol. How this translates into number of drinks depends
on portion size (the standards of which differ per country), I B
but most drinks contain 8–14 g of alcohol per drink.
Preferably, it is recommended to avoid alcohol to achieve
the best health outcomes.
It is recommended to restrict free sugar consumption, in
particular sugar-sweetened beverages, to a maximum of
10% of energy intake.
I B
It is also recommended to discourage consumption of sugar-
sweetened beverages, such as soft drinks and fruit juices,
starting at young age.
It is recommended to stop tobacco smoking, initiate
supportive care and refer to smoking cessation
I A
programmes, as tobacco use strongly and independently
causes CVD, CVD events, and all-cause mortality.

43
 In patients with hypertension without moderate to
advanced CKD and with high daily sodium intake, an
increase of potassium intake by 0.5–1.0 g/day—for example
through sodium substitution with potassium-enriched salt IIa A
(comprising 75% sodium chloride and 25% potassium
chloride) or through diets rich in fruits and vegetables—
should be considered.
In patients with CKD or taking potassium-sparing
medication, such as some diuretics, ACE inhibitors, ARBs,
IIa C
or spironolactone, monitoring serum levels of potassium
should be considered if dietary potassium is being increased.
ACE, angiotensin-converting enzyme; ARB, angiotensin receptor blocker;
BMI, body mass index; BP, blood pressure; CKD, chronic kidney disease;
CVD, cardiovascular disease; DASH, Dietary Approaches to Stop
Hypertension.

Pharmacological interventions

There is a clear relationship between the intensity of BP lowering and the

relative and absolute reduction in risk of CVD events for all adults,
regardless of age (at least up to 85 years), sex, prior CVD, diabetes, or
atrial fibrillation. With this strong evidence for the ‘the lower the better,
but within reason’ paradigm, decision rules are required for selecting
patients most likely to benefit from treatment.
As highlighted in the algorithm in Figure 18, it is recommended to
introduce a low-dose double- and then triple-combination strategy while
monitoring tolerance among patients with hypertension, and only
afterwards to start up-titrating doses to maximum amounts. Initiation
with monotherapy, slower up-titration, and lower dosing should be
considered in the setting of elevated BP and increased CVD risk, or in
moderate-to-severe frailty, limited life expectancy, symptomatic
orthostatic hypotension, or older people (≥85 years). Ideally, BP should
be treated to target within 3 months to retain the confidence of the
patient, to ensure long-term adherence, and to reduce CVD risk.
An overview of the recommended approach to BP management in all
adult patients is provided in Figure 19. Teleconsultation,
multidisciplinary or nurse-led care, or patient self-monitoring can help
with achieving BP control in certain healthcare systems.

44
Figure 18 Practical algorithm for pharmacological BP lowering.

ACEi, angiotensin-converting enzyme inhibitor; ARB, angiotensin receptor

blocker; BP, blood pressure; CCB, calcium channel blocker; FU, follow-up.

45
Figure 19 Central Illustration.

46
ABPM, ambulatory blood pressure monitoring; BP, blood pressure; DBP,
diastolic blood pressure; HBPM, home blood pressure monitoring; OBP,
office blood pressure; OH, orthostatic hypotension; SBP, systolic blood
pressure; SCORE2, Systematic COronary Risk Evaluation 2; SCORE2-OP,
Systematic COronary Risk Evaluation 2 – Older Persons. See Section 5
of full guidelines for recommendations on out-of-office confirmation of
the three BP categories.
a
Adults with type 2 diabetes younger than 60 years should be considered
for SCORE2-Diabetes assessment.
b
Though scientific data demonstrate that, under research conditions, the
optimal target BP is ≤120/70 mmHg, the target BP recommended by
these Guidelines in routine clinical practice is 120–129/70–79 mmHg. If
achieving this target is not possible, or if treatment is not well tolerated,
then BP should be treated to as low as reasonably achievable. For
persons with elevated BP, treatment with lifestyle for 3 months is first
recommended, prior to considering medications.

Recommendations for pharmacological treatment of hypertension

Recommendations Class Level

Among all BP-lowering drugs, ACE inhibitors, ARBs,

dihydropyridine CCBs, and diuretics (thiazides and
thiazide-like drugs such as chlorthalidone and
I A
indapamide) have demonstrated the most effective
reduction of BP and CVD events, and are therefore
recommended as first-line treatments to lower BP.

It is recommended that beta-blockers are combined with

any of the other major BP-lowering drug classes when
there are other compelling indications for their use, e.g. I A
angina, post-myocardial infarction, heart failure with
reduced ejection fraction, or for heart rate control.

It is recommended to take medications at the most

convenient time of day for the patient to establish a
I B
habitual pattern of medication taking to improve
adherence.

47
 Given trial evidence for more effective BP control vs.
monotherapy, combination BP-lowering treatment is
recommended for most patients with confirmed
hypertension (BP ≥140/90 mmHg) as initial therapy.
Preferred combinations are a RAS blocker (either
an ACE inhibitor or an ARB) with a
I B
dihydropyridine CCB or diuretic. Exceptions to consider
include patients aged ≥85 years, those with symptomatic
orthostatic hypotension, moderate-to-severe frailty, or
elevated BP (systolic BP 120–139 mmHg or
diastolic BP 70–89 mmHg) with a concomitant indication
for treatment.

In patients receiving combination BP-lowering treatment,

fixed-dose single-pill combination treatment is I B
recommended.

If BP is not controlled with a two-drug combination,

increasing to a three-drug combination is recommended,
usually a RAS blocker with a dihydropyridine CCB and a I B
thiazide/thiazide-like diuretic, and preferably in a single-
pill combination.

If BP is not controlled with a three-drug combination,

IIa B
adding spironolactone should be considered.

If BP is not controlled with a three-drug combination and

in whom spironolactone is not effective or tolerated,
treatment with eplerenone instead of spironolactone, or
the addition of a beta-blocker if not already indicated IIa B
and, next, a centrally acting BP-lowering medication, an
alpha-blocker, or a potassium-sparing diuretic should be
considered.

Combining two RAS blockers (ACE inhibitor and an

III A
ARB) is not recommended.
ACE, angiotensin-converting enzyme; ARB, angiotensin receptor blocker;
BP, blood pressure; CCB, calcium channel blocker; CVD, cardiovascular
disease; RAS, renin–angiotensin system.

48
Selecting patients for pharmacological blood pressure
lowering treatment
In individuals with elevated BP, further CVD risk stratification is recommended
to select those requiring BP-lowering treatment, whereas in individuals with
confirmed hypertension BP-lowering treatment is always indicated (Table 9).

Table 9 Initiation of blood pressure-lowering treatment based on

confirmed blood pressure category and cardiovascular disease risk

49
BP, blood pressure; CKD, chronic kidney disease; CVD, cardiovascular
disease; DBP, diastolic blood pressure; FH, familial
hypercholesterolaemia; HMOD, hypertension-mediated target organ
damage; SBP, systolic blood pressure.
a
Caution in adults with orthostatic hypotension, moderate-to-severe
frailty, limited life expectancy, and older patients (aged ≥85 years).

Recommendations for initiating blood pressure-lowering treatment

Recommendations Class Level

In adults with elevated BP and low/medium CVD risk

(<10% over 10 years), BP lowering with lifestyle
I B
measures is recommended and can reduce the risk
of CVD.

In adults with elevated BP and sufficiently

high CVD riska, after 3 months of lifestyle
intervention, BP lowering with pharmacological I A
treatment is recommended for those with
confirmed BP ≥130/80 mmHg to reduce CVD risk.

It is recommended that in hypertensive patients with

confirmed BP ≥140/90 mmHg, irrespective of CVD risk,
I A
lifestyle measures and pharmacological BP-lowering
treatment are initiated promptly to reduce CVD risk.

It is recommended to maintain BP-lowering drug

treatment lifelong, even beyond the age of 85 years, if well I A
tolerated.

Because the benefit in reducing CVD outcomes is

uncertain in these settings, and noting that close
monitoring of treatment tolerance is advised, BP-
lowering treatment should only be considered from ≥140/
IIa B
90 mmHg among persons meeting the following criteria:
pre-treatment symptomatic orthostatic hypotension, age
≥85 years, clinically significant moderate-to-severe
frailty, and/or limited predicted lifespan (<3 years).
BP, blood pressure; CVD, cardiovascular disease
a
10-year estimated CVD risk ≥10% or high-risk conditions (e.g.
established CVD, diabetes, moderate or severe CKD, familial
hypercholesterolaemia, or hypertension-mediated target organ damage).

50
Intensity of BP lowering therapy and ideal treatment targets

The ideal target of BP lowering treatment

Blood pressure threshold is defined as the BP at which BP-lowering treatment is

initiated, while BP target is the BP goal to be achieved with treatment. The two may
not be the same for a given patient.
In the 2024 Guidelines, the treatment target is always 120–129/70–79 mmHg.
Exceptions are intolerance to treatment, as well as symptomatic orthostatic
hypotension, age>85 years, moderate-to-severe frailty at any age, and limited
predicted lifespan: in those conditions, BP should be treated to as low as reasonably
achievable and more lenient targets are advised (Figure 20 and Table 9). By contrast,
the treatment threshold may differ based on CVD risk, specifically in the
elevated BP category (Table 9).

Figure 20 Systolic BP categories and treatment target range.

BP, blood pressure; SBP, systolic blood pressure.

51
 Recommendations for BP targets with treatment

Recommendations Class Level

To reduce CVD risk, it is recommended that treated

systolic BP values in most adults be targeted to 120–129 I A
mmHg, provided the treatment is well tolerated.

In cases where BP-lowering treatment is poorly tolerated

and achieving a systolic of 120–129 mmHg is not possible,
I A
it is recommended to target a systolic BP level that is ‘as
low as reasonably achievable’ (ALARA principle).

Because the CVD benefit of an on-treatment

systolic BP target of 120–129 mmHg may not generalize
to the following specific settings, personalized and more
lenient BP targets (e.g. <140 mmHg) should be considered IIa C
among patients meeting the following criteria: pre-
treatment symptomatic orthostatic hypotension, and/or
age ≥85 years.

Because the CVD benefit of an on-treatment

systolic BP target of 120–129 mmHg may not generalize
to the following specific settings, personalized and more
lenient BP targets (e.g. <140/90 mmHg) may be IIb C
considered among patients meeting the following criteria:
clinically significant moderate-to-severe frailty at any
age, and/or limited predicted lifespan (<3 years).

In cases where on-treatment systolic BP is at or below

target (120–129 mmHg) but diastolic BP is not at target
(≥80 mmHg), intensifying BP-lowering treatment to IIb C
achieve an on-treatment diastolic BP of 70–79 mmHg
may be considered to reduce CVD risk.
ALARA, as low as reasonably achievable; BP, blood pressure; CVD,
cardiovascular disease.

52
Duration and monitoring of drug therapy

Recommendations for clinical and diagnostic tools for patients with

suspected acute coronary syndrome

Recommendations Class Level

Once BP is controlled and stable under BP-lowering

therapy, at least a yearly follow-up for BP and IIa C
other CVD risk factors should be considered.
BP, blood pressure; CVD, cardiovascular disease.

53
Device based blood pressure lowering

Recommendations for clinical and diagnostic tools for patients with

suspected acute coronary syndrome

Recommendations Class Level

To reduce BP, and if performed at a medium-to-high

volume centre, catheter-based renal denervation may be
considered for resistant hypertension patients who
have BP that is uncontrolled despite a three BP-lowering
IIb B
drug combination (including a thiazide or thiazide-like
diuretic), and who express a preference to undergo renal
denervation after a shared risk-benefit discussion and
multidisciplinary assessment.

To reduce BP, and if performed at a medium-to-high

volume centre, catheter-based renal denervation may be
considered for patients with both increased CVD risk and
uncontrolled hypertension on fewer than three drugs, if IIb A
they express a preference to undergo renal denervation
after a shared risk-benefit discussion and
multidisciplinary assessment.

Due to a lack of adequately powered outcomes trials

demonstrating its safety and CVD benefits, renal
III C
denervation is not recommended as a first-line BP-
lowering intervention for hypertension.

Renal denervation is not recommended for treating

hypertension in patients with moderate-to-severely
impaired renal function (eGFR <40 mL/min/1.73 m2) or III C
secondary causes of hypertension, until further evidence
becomes available.
BP, blood pressure; CVD, cardiovascular disease; eGFR, estimated
glomerular filtration rate.

54
Managing specific patient groups or
circumstances

Young adulthood 18-40 years

Irrespective of cardiovascular risk, all young adults with elevated BP are

recommended to follow lifestyle guidance for BP lowering. A discussion
about family planning should be taken with young women of
childbearing potential at each visit. Adherence to treatment is low in
young adults, <50% in some studies. communicating the importance of
adherence, education, and follow-up clinics is important.

Recommendations for managing hypertension in young adults

Recommendations Class Level

Comprehensive screening for the main causes of

secondary hypertension is recommended in adults
diagnosed with hypertension before the age of 40 years, I B
except for obese young adults where it is recommended to
start with an obstructive sleep apnoea evaluation.

Since SCORE2 has not been validated for individuals <40

years, screening for HMOD may be considered in
individuals with elevated BP without other IIb B
increased CVD risk conditions to identify additional
individuals for medical treatment.
BP, blood pressure; CVD, cardiovascular disease; HMOD, hypertension-
mediated target organ damage; SCORE2, Systematic COronary Risk
Evaluation 2.

55
Pregnancy

Definition and epidemiology

Hypertension in pregnancy is typically defined as systolic BP ≥140

mmHg and/ or diastolic BP ≥90 mmHg measured using
repeated BP readings in the office or hospital on two separate occasions
or ≥15 min apart in severe hypertension (≥160/110 mmHg).
Hypertension in pregnancy is the second leading cause of maternal
death after maternal peri-partum haemorrhage. Approximately 7% of
pregnancies are complicated by hypertension, of which 3% are due to
pre-eclampsia and around 1% are chronic or pre-existing hypertension.
Women with a history of hypertensive disorders during pregnancy are at
increased risk of subsequent hypertension and CVD.

Risk of recurrence of hypertensive disorders in a

subsequent pregnancy

About 20–30% of women with hypertensive disorders in a previous

pregnancy will experience recurrence in a subsequent pregnancy. The
earlier the onset of hypertension in the first pregnancy, the higher the
risk of recurrence in a subsequent pregnancy.

56
Recommendations for managing hypertension in pregnancy

Recommendations Class Level

In women with gestational hypertension, starting drug

treatment is recommended for those with confirmed I B
office systolic BP ≥140 mmHg or diastolic BP ≥90 mmHg.

In pregnant women with chronic hypertension, starting

drug treatment is recommended for those with confirmed I B
office systolic BP ≥140 mmHg or diastolic BP ≥90 mmHg.

In women with chronic and gestational hypertension, it is

recommended to lower BP below 140/90 mmHg but not I C
below 80 mmHg for diastolic BP.

Dihydropyridine CCBs (preferably extended-release

nifedipine), labetalol, and methyldopa are recommended
I C
first-line BP-lowering medications for treating
hypertension in pregnancy.

In consultation with an obstetrician, low- to moderate-

intensity exercise is recommended in all pregnant women
I B
without contraindications to reduce the risk of gestational
hypertension and pre-eclampsia.

Systolic BP ≥160 mmHg or diastolic BP ≥110 mmHg in

pregnancy can indicate an emergency, and immediate IIa C
hospitalization should be considered.

HBPM and ABPM should be considered to exclude white

coat and masked hypertension, which are more common IIa C
in pregnancy.

RAS blockers are not recommended during pregnancy. III B

ABPM, ambulatory blood pressure monitoring; BP, blood pressure; CCB,
calcium channel blocker; HBPM, home blood pressure monitoring; RAS,
renin–angiotensin system.

57
Maintaining BP lowering in very old or frail patients
If very old and frail patients tolerate BP-lowering treatment well, there is no
automatic need to deprescribe or discontinue treatment; however, this should be
kept under review.
Recommendations for managing hypertension in patients who are
very old or frail
Recommendations Class Level
It is recommended that treatment of elevated BP and
hypertension among older patients aged <85 years who are
not moderately to severely frail follows the same guidelines I A
as for younger people, provided BP-lowering treatment is
well tolerated.
It is recommended to maintain BP-lowering drug treatment
I A
lifelong, even beyond the age of 85 years, if well tolerated.
Because the benefit in reducing CVD outcomes is uncertain
in these settings, and noting that close monitoring of
treatment tolerance is advised, BP-lowering treatment
should only be considered from ≥140/90 mmHg among
IIa B
persons meeting the following criteria: pre-treatment
symptomatic orthostatic hypotension, age ≥85 years,
clinically significant moderate-to-severe frailty, and/or
limited predicted lifespan (<3 years).
As the safety and efficacy of BP treatment is less certain in
individuals with moderate or severe frailty, clinicians should
consider screening older adults for frailty using validated
IIa C
clinical tests; frail patients’ health priorities and a shared-
decision approach should be considered when deciding
on BP treatments and targets.
When initiating BP-lowering treatment for patients aged ≥85
years, and/or with moderate-to-severe frailty (at any age),
long-acting dihydropyridine CCBs or RAS inhibitors should
IIa B
be considered, followed if necessary by low dose-diuretic if
tolerated, but preferably not a beta-blocker (unless
compelling indications exist) or an alpha-blocker.
If BP drops with progressing frailty, deprescription of BP-
lowering medications (and other drugs that can reduce BP,
IIb C
such as sedatives and prostate-specific alpha-blockers) may
be considered.
BP, blood pressure; CCB, calcium channel blocker; CVD, cardiovascular disease; RAS, renin–
angiotensin system.

58
Orthostatic hypotension with supine hypertension
Recommendations for managing hypertension in patients with
orthostatic hypotension
Recommendations Class Level

Before starting or intensifying BP-lowering medication, it is

recommended to test for orthostatic hypotension, by first
I B
having the patient sit or lie for 5 minutes and then
measuring BP 1 and/or 3 minutes after standing.
It is recommended to pursue non-pharmacological
approaches as the first-line treatment of orthostatic
hypotension among persons with supine hypertension. For
such patients, it is also recommended to switch BP-lowering I A
medications that worsen orthostatic hypotension to an
alternative BP-lowering therapy and not to simply de-
intensify therapy.
BP, blood pressure.

Diabetes

Recommendations for managing hypertension in patients with

diabetes
Recommendations Class Level

In adults with elevated BP and diabetes, after a maximum

of 3 months of lifestyle intervention, BP lowering with
I A
pharmacological treatment is recommended for those with
confirmed office BP ≥130/80 mmHg to reduce CVD risk.
BP-lowering drug treatment is recommended for people
with pre-diabetes or obesity when confirmed office BP is
≥140/90 mmHg or when office BP is 130–139/80–89 mmHg
I A
and the patient is at predicted 10-year risk of CVD ≥10% or
with high-risk conditions, despite a maximum of 3 months
of lifestyle therapy.
In persons with diabetes who are receiving BP-lowering
drugs, it is recommended to target systolic BP to 120–129 I A
mmHg, if tolerated.
BP, blood pressure; CVD, cardiovascular disease.

59
Chronic kidney disease

Recommendations for managing hypertension in patients with

chronic kidney disease

Recommendations Class Level

In patients with diabetic or non-diabetic moderate-to-

severe CKD and confirmed BP ≥130/80 mmHg, lifestyle
optimization and BP-lowering medication are I A
recommended to reduce CVD risk, provided such
treatment is well tolerated.

In adults with moderate-to-severe CKD who are

receiving BP-lowering drugs and who have eGFR >30
mL/min presented everywhere else as mL/min/1.73 m2, it
I A
is recommended to target systolic BP to 120–129 mmHg,
if tolerated. Individualized BP targets are recommended
for those with lower eGFR or renal transplantation.

In hypertensive patients with CKD and eGFR >20 mL/

min/1.73 m2, SGLT2 inhibitors are recommended to
I A
improve outcomes in the context of their modest BP-
lowering properties.

ACE inhibitors and ARBs are more effective at reducing

albuminuria than other BP-lowering agents and should
be considered as part of the treatment strategy for IIa B
patients with hypertension and microalbuminuria or
proteinuria.
ACE, angiotensin-converting enzyme; ARB, angiotensin receptor blocker;
BP, blood pressure; CKD, chronic kidney disease, eGFR, estimated
glomerular filtration rate; SGLT2, sodium–glucose co-transporter 2.

60
Cardiac disease

Recommendations for managing hypertension in patients with

cardiac disease
Recommendations Class Level

In patients with a history of myocardial infarction who

require BP-lowering treatment, beta-blockers
I A
and RAS blockers are recommended as part of that
treatment.
In patients with symptomatic angina who require BP-
lowering treatment, beta-blockers and/or CCBs are I A
recommended as part of that treatment.
In patients with symptomatic HFrEF/HF(m)rEF, the
following treatments with BP-lowering effects are
recommended to improve outcomes: ACE inhibitors (or I A
ARBs if ACE inhibitors are not tolerated) or ARNi, beta-
blockers, MRAs, and SGLT2 inhibitors.
In hypertensive patients with symptomatic
HFpEF, SGLT2 inhibitors are recommended to improve I A
outcomes in addition to their modest BP-lowering properties.
In patients with a history of aortic valve stenosis and/or
regurgitation who require BP-lowering
IIa C
treatment, RAS blockers should be considered as part of that
treatment.
In patients with a history of moderate-severe mitral valve
regurgitation who require BP-lowering
IIa C
treatment, RAS blockers should be considered as part of that
treatment.
In patients with symptomatic HFpEF who have BP above
target, ARBs and/or MRAs may be considered to reduce IIb B
heart failure hospitalizations and reduce BP.
ACE, angiotensin-converting enzyme; ARB, angiotensin receptor blocker; ARNi,
angiotensin receptor-neprilysin inhibitor; BP, blood pressure; CCB, calcium channel
blocker; HFpEF, heart failure with preserved ejection fraction; HF(m)rEF, heart failure
with (minimally) reduced ejection fraction; MRA, mineralocorticoid receptor
antagonist; RAS, renin–angiotensin system; SGLT2, sodium–glucose co-transporter
2.

61
Chronic cerebrovascular disease and or cognitive
impairment

Recommendations for managing hypertension in patients with

chronic cerebrovascular disease and cognitive impairment

Recommendations Class Level

It is recommended that the BP-lowering drug treatment

strategy for preventing recurrent stroke should comprise I A
a RAS blocker plus a CCB or a thiazide-like diuretic.

In patients with confirmed BP ≥130/80 mmHg with a

history of TIA or stroke a systolic BP target of 120–129
I A
mmHg is recommended to reduce CVD outcomes,
provided treatment is tolerated.
BP, blood pressure; CCB, calcium channel blocker; CVD, cardiovascular
disease; RAS, renin–angiotensin system; TIA, transient ischaemic attack.

Different ethnic groups

Influx and settlement of migrant populations in Europe have contributed
to regional population growth and changes in its composition. Ethnic
minority populations are disproportionally affected by hypertension and
hypertension-mediated complications, compared with historically native
Europeans, with data suggesting migrant women are particularly
vulnerable.
Despite some recent progress, data on hypertension epidemiology and
management in European immigrant patients are mostly lacking.

Recommendation for managing hypertension in different ethnic

groups

Recommendations Class Level

In black patients from Sub-Saharan Africa who

require BP-lowering treatment, combination therapy
IIa B
including a CCB combined with either a thiazide diuretic
or a RAS blocker should be considered.
BP, blood pressure; CCB, calcium channel blocker; RAS, renin–angiotensin system.

62
Resistant hypertension
Figure 21 Management of resistant hypertension.

BP, blood pressure; K+, potassium; SPC, single-pill combination.

63
Management of specific causes of secondary
hypertension - renovascular hypertension
These Guidelines describe only the general principles of managing the
most common forms of secondary hypertension (Figure 13, Figure
14, Figure 15). For the rarer forms of secondary hypertension, patients
should be referred to specialized hypertension centres.

Recommendations for managing hypertension in patients with

renovascular hypertension
Recommendations Class Level

Renal artery angioplasty without stenting should be

considered for patients with haemodynamically significant
IIa C
renal artery stenosis due to fibromuscular dysplasia and
hypertension.
Renal artery angioplasty and stenting may be considered in
patients with haemodynamically significant, atherosclerotic,
renal artery stenosis (stenosis of 70–99%, or 50–69% with
post-stenotic dilatation and/or significant trans-stenotic
pressure gradient) with:
Recurrent heart failure, unstable angina, sudden-onset flash
pulmonary oedema despite maximally tolerated medical IIb C
therapy.
Resistant hypertension.
Hypertension with unexplained unilaterally small kidney
or CKD.
Bilateral renal artery stenosis or unilateral renal artery
stenosis in a solitary viable kidney.
In patients with an indication to renal artery
revascularization and technically unfeasible, or failed, renal
IIb C
artery angioplasty and stenting, open surgical
revascularization may be considered.
Renal artery angioplasty is not recommended in patients
without confirmed haemodynamically significant renal III A
artery stenosis.a
CKD, chronic kidney disease.
a
A haemodynamically relevant stenosis is usually defined by a luminal
narrowing >70% or 50–70% with poststenotic dilatation.

64
Acute and short term lowering of BP

Acute BP management in acute ischaemic stroke

Recommendations for acutely managing BP in patients with

intracerebral haemorrhage or acute ischaemic stroke

Recommendations Class Level

For patients with ischaemic stroke or TIA and an

indication for BP lowering, it is recommended that BP-
I B
lowering therapy be commenced before hospital
discharge.
In patients with acute ischaemic stroke, early BP lowering with BP-lowering
therapy should be considered in the first 24 h in the following settings:

In patients who are eligible for re-perfusion therapy with

intravenous thrombolysis or mechanical
thrombectomy, BP should be carefully lowered and IIa B
maintained at <180/105 mmHg for at least the first 24 h
after treatment.

In patients with ischaemic stroke not receiving re-

perfusion treatment and BP of ≥220/110
mmHg, BP should be carefully lowered by IIa C
approximately 15% during the first 24 h after stroke
onset.

In patients with intracerebral haemorrhage,

immediate BP lowering (within 6 hours of symptom
onset) should be considered to a systolic target 140–160 IIa A
mmHg to prevent haematoma expansion and improve
functional outcome.

In patients with intracerebral haemorrhage presenting

with systolic BP ≥220 mmHg, acute reduction in
III B
systolic BP >70 mmHg from initial levels within 1 hour of
commencing treatment is not recommended.
BP, blood pressure; TIA, transient ischaemic attack.

65
Acute BP management in pre eclampsia and
severe hypertension in pregnancy

In the acute setting, pre-eclampsia is cured by delivery. In women with

pre-eclampsia and severe hypertension, immediately reducing
systolic BP to <160 mmHg and diastolic BP to <105 mmHg using i.v.
labetalol or nicardipine (with administration of magnesium sulphate and
consideration of delivery if appropriate) is recommended with the
objective to lower BP within 150–180 minutes. Severe hypertension in
pregnancy is defined as systolic BP >160 mmHg and diastolic BP >110
mmHg and is associated with adverse maternal and perinatal outcomes
independent of pre-eclampsia, thus it necessitates acute BP-lowering
too.

Recommendations for acutely managing BP in patients with severe

hypertension in pregnancy and pre-eclampsia

Recommendations Class Level

In eclampsia, drug treatment with i.v. labetalol or

I C
nicardipine and magnesium is recommended.

In pre-eclampsia or eclampsia associated with pulmonary

oedema, nitroglycerin given as an i.v. infusion is I C
recommended.

In severe hypertension in pregnancy, drug treatment

with i.v. labetalol, oral methyldopa, or oral nifedipine is
I C
recommended. Intravenous hydralazine is a second-line
option.
i.v, intravenous.

66
Patient centred care in hypertension

Overview
Patient-centred care is defined as an attitude of the healthcare
professional that closely aligns with the patient’s preferences and
needs. In the patient-centred approach (Figure 22), patients are viewed
as active participants in health services, who work as partners. A patient-
centred approach is associated with higher satisfaction rates, better
adherence to recommendations and prescriptions, and better treatment,
particularly in the management of chronic illness, such as hypertension.
Figure 22 Patient-centred care.

67
Standard approaches to communicate consequences of treatment can
involve 10-year risk of a CVD event with SCORE2 or SCORE2-OP.
Alternatively, individual risk and risk reduction can be communicated in
terms of ‘risk age’ or ‘heart age’.

Recommendations for communicating consequences of treatment

Recommendations Class Level

An informed discussion about CVD risk and treatment

benefits tailored to the needs of a patient is recommended I C
as part of hypertension management.

Motivational interviewing should be considered for

patients with hypertension at hospitals and community
IIa B
health centres to assist patients in controlling
their BP and to enhance treatment adherence.

Physician–patient web communications are an effective

tool that should be considered in primary care, including IIa C
reporting on home BP readings.
BP, blood pressure; CVD, cardiovascular disease.

Self measuring and monitoring

Recommendations for self-measuring and monitoring BP

Recommendations Class Level

Home BP measurement for managing hypertension by

using self- monitored BP is recommended to achieve I B
better BP control

Self-measurement, when properly performed, is

recommended due to positive effects on the acceptance of
I C
a diagnosis of hypertension, patient empowerment, and
adherence to treatment.

Enhanced self-monitoring of BP using a device paired

with a connected smartphone application may be
IIb B
considered, though evidence to date suggests that this
may be no more effective than standard self-monitoring.
BP, blood pressure.

68
Facilitating medication adherence and
persistence
Adherence (Figure 23) to BP-lowering drug regimens in clinical practice
is often lower than in clinical trials. Most apparent treatment-resistant
hypertension is accounted for by non-adherence Adherence should
always be assessed with a no- blame approach.
Figure 23 The five dimensions of adherence (WHO, 2003)
applied to hypertension.

69
Multidisciplinary management

A collaborative approach to managing hypertension, using team-based

care among physicians, nurses, pharmacists, dietitians, and
physiotherapists, offers significant benefits over physician-only care.
Multidisciplinary care is intended to be collaborative and complementary
to regular medical care and is associated with lower SBP and DBP and
improved outcomes. Task-shifting away from physicians is necessary to
meet the huge need for the management of elevated BP and
hypertension in the population. Prescribing remains a physician duty, but
prescribing can be conducted under collaborative practice agreements
with the multidisciplinary team in many countries.

Recommendation for multi/interdisciplinary blood pressure

management

Recommendations Class Level

Multidisciplinary approaches in the management of

patients with elevated BP and hypertension, including
I A
appropriate and safe task- shifting away from physicians,
are recommended to improve BP control.
BP, blood pressure.

70
Table of Contents
Essential Messages .................................................................................................. 1
Authors and legal information .............................................................................. 1
Key messages ........................................................................................................ 2
Gaps in evidence ................................................................................................... 5
Authors and legal information ................................................................................. 6
Preamble .................................................................................................................. 7
Introduction ............................................................................................................. 8
Epidemiology and risk factors .................................................................................. 9
Evaluation of peripheral arteries and aorta ........................................................... 10
Overview ............................................................................................................. 10
Vascular examination of peripheral arteries....................................................... 11
Evaluation of the aorta ....................................................................................... 13
Screening for carotid peripheral arterial, and aortic diseases ............................... 15
Optimal medical treatment ................................................................................... 16
Peripheral arterial disease ..................................................................................... 21
Lower extremity PAD .......................................................................................... 21
PAD syndromes and treatments ...................................................................... 21
Chronic limb threatening ischaemia ................................................................ 32
Acute limb ischaemia ....................................................................................... 33
Extracranial carotid and vertebral artery disease ............................................... 36
Overview .......................................................................................................... 36
Asymptomatic carotid artery stenosis ............................................................. 38
Symptomatic carotid artery stenosis ............................................................... 41
Other arterial locations ....................................................................................... 43
Subclavian artery disease ................................................................................ 43
Renal artery disease......................................................................................... 44
 Visceral artery disease ..................................................................................... 47
Aorta ...................................................................................................................... 50
Atheromatous disease of the aorta .................................................................... 50
Aortic aneurysms ................................................................................................ 51
General concepts ............................................................................................. 51
Thoracic aortic aneurysms ............................................................................... 51
Abdominal aortic aneurysms ........................................................................... 54
Optimal medical treatment of aortic aneurysms............................................. 55
Surgical management of aortic aneurysms ..................................................... 55
Endoleaks ......................................................................................................... 60
Long term follow up after aortic repair ........................................................... 60
Acute thoracic aortic syndromes ........................................................................ 62
General concepts ............................................................................................. 62
Intramural haematoma.................................................................................... 70
Penetrating atherosclerotic ulcer .................................................................... 71
Traumatic aortic injury .................................................................................... 72
Long term follow up of acute aortic syndrome ............................................... 73
Genetic and congenital diseases of the aorta ........................................................ 74
Genetic and chromosomal diseases ................................................................... 74
Overview .......................................................................................................... 74
Turner syndrome ............................................................................................. 77
Vascular Ehlers Danlos syndrome .................................................................... 78
Marfan syndrome ............................................................................................ 79
Loeys Dietz syndrome ...................................................................................... 84
Aortic disease associated with bicuspid aortic valves......................................... 87
Polyvascular PAD and PAD in patients with cardiac diseases ................................ 88
Essential Messages

Authors and legal information

2024 ESC Guidelines for the management of peripheral arterial and aortic diseases
Developed by the task force on the management of peripheral arterial and aortic diseases of the European Society of
Cardiology (ESC)
Endorsed by the European Association for Cardio-Thoracic Surgery (EACTS), the European Reference Network on
Rare Multisystemic Vascular Diseases (VASCERN), and the European Society of Vascular Medicine (ESVM)

Chairpersons
Lucia Mazzolai
Department of Angiology, Centre
Hospitalier Universitaire Vaudois
(CHUV), and Faculty of Biology and
Medicine (FBM), University of
Lausanne (UNIL) Lausanne,
Switzerland
Jose F. Rodriguez-Palomares
Cardiovascular Imaging section and Aortic
diseases Unit (VASCERN), Department of
Cardiology, Vall d’Hebron Hospital
Universitari, Vall d’Hebron Barcelona Hospital
Campus, Vall d′Hebron Institut de Recerca
(VHIR), Barcelona, and Centro de
Investigación Biomédica en Red de
Enfermedades Cardiovasculares, Instituto de
Salud Carlos III, Madrid, and Department of
Medicine, Universitat Autònoma de Barcelona,
Spain
Task Force Members:
Gisela Teixido-Tura (Task Force Co-ordinator) (Spain), Stefano Lanzi (Task Force Co-ordinator) (Switzerland), Vinko
Boc (Slovenia), Eduardo Bossone (Italy), Marianne Brodmann1 (Austria), Alessandra Bura-Rivière (France), Julie De
Backer2 (Belgium), Sebastien Deglise) (Switzerland), Alessandro Della Corte (Italy), Christian Heiss (United Kingdom),
Marta Kałużna-Oleksy (Poland), Donata Kurpas (Poland), Carmel M. McEniery (United Kingdom), Tristan Mirault
(France), Agnes A. Pasquet (Belgium), Alex Pitcher (United Kingdom), Hannah A.I. Schaubroeck (Belgium), Oliver
Schlager) (Austria), Per Anton Sirnes (Norway), Muriel G. Sprynger (Belgium), Eugenio Stabile (Italy), Françoise
Steinbach (France), Matthias Thielmann (Germany), Roland R.J. van Kimmenade (Netherlands), Maarit Venermo
(Finland).
1Representing the European Society of Vascular Medicine (ESVM).
2Representing the European Reference Network on Rare Multisystemic Vascular Diseases (VASCERN).

ESC subspeciality communities having participated in the development of this document:

Associations: Association for Acute CardioVascular Care (ACVC), Association of Cardiovascular Nursing & Allied
Professions (ACNAP), European Association of Cardiovascular Imaging (EACVI), European Association of Preventive
Cardiology (EAPC), European Association of Percutaneous Cardiovascular Interventions (EAPCI), Heart Failure
Association (HFA).
Councils: Council for Cardiology Practice, Council on Hypertension.
Working Groups: Adult Congenital Heart Disease, Aorta and Peripheral Vascular Diseases, Cardiovascular Surgery,
Thrombosis.
Patient forum
Adapted from the 2024 ESC Guidelines for the management of peripheral arterial and aortic diseases European Heart
Journal; 2024 – doi:10.1093/eurheartj/ehae179

1
Key messages

Peripheral arterial and aortic diseases are highly prevalent, often

asymptomatic, and linked to increased morbidity and mortality.
Early diagnosis is crucial for better outcomes and management
requires a multidisciplinary team. CVRF control is crucial to
prevent progression and complications. Despite the benefit of
medical therapy, lifestyle changes, healthy diet, abstinence from
smoking, exercise/rehabilitation, and education are essential for
effective management. Patient empowerment is essential to
improve adherence and close/regular monitoring is essential to
improve prognosis. Use of web- or app-based calculators for
estimation of CV risk in the secondary prevention of ASCVD may
aid patient motivation for lifestyle changes and adherence to
medication.

Peripheral arteries
1. Atherosclerotic lower-extremity PAD is a chronic disease
needing lifelong follow-up.
2. Assessment of walking impairment, functional status, and
amputation risk is crucial in PAD management.
3. ABI should be the initial diagnostic test for screening and
diagnosing PAD, and serves as a surrogate marker for CV and
all-cause mortality. DUS is the first-line imaging method to
confirm PAD lesions.
4. SET or, if not available, HBET, improves walking and functional
performances, and reduces CV risk. Exercise training remains
underused and increased awareness is warranted.
5. In asymptomatic PAD patient revascularization is not
recommended. In symptomatic PAD patient need for
interventional treatment, following a period of optimal medical

2
 treatment and exercise, should be discussed in a
multidisciplinary setting.
6. CLTI increases the risk of CV events, needs early diagnosis,
rapid referral to a multidisciplinary vascular team, and
revascularization for limb salvage.
7. ALI warrants rapid clinical assessment by a vascular team and
urgent revascularization.
8. DUS is the first-line diagnostic modality for carotid stenosis.
Routine revascularization is not recommended if
asymptomatic. In symptomatic patients multidisciplinary
assessment is recommended.
9. Atherosclerotic UEAD is most frequently located in the
subclavian artery and may be suspected because of an
absolute inter-arm SBP difference >10–15 mmHg. DUS is first-
line imaging and routine revascularization is not
recommended.
10. The key to early diagnosis of acute and chronic mesenteric
ischaemia is a high level of clinical suspicion—laboratory tests
are unreliable for the diagnosis. Acute SMA occlusion requires
immediate revascularization.

Aorta
1. Aortic aneurysms are managed based on size, location, and
growth rate. Small aneurysms are monitored regularly
(guidelines provide disease-specific follow-up algorithms),
while larger ones may require surgical/endovascular repair to
prevent rupture.
2. In aortic root aneurysms, aortic replacement may be
considered at >52 mm in low-risk patients and at experienced
centres.
3. Aortic diameter is the primary risk factor for aortic events.
However, evidence supports diameter indexation (especially in

3
 extreme BSA populations) and the use of aortic length (>11
cm), the AHI (>32.1 mm/m), growth rate (≥3 mm per year for
ascending aorta and arch or >5 mm per 6 months in the
thoracoabdominal aorta), and age/sex for risk assessment.
4. Multidisciplinary collaboration, hybrid operating rooms, and
advanced stent technology have increased the adoption of
hybrid approaches and endovascular therapies for different
thoracoabdominal aortic diseases.
5. Acute aortic syndrome management involves medical
treatment in critical care units and selective surgical
intervention based on location and complications. The main
problem in these conditions continues to be a delay in
diagnosing patients or transferring them to an aortic centre.
Improved diagnostic algorithms and reduced surgical
complications have lowered mortality rates. Surgical/
endovascular treatment in the subacute phase is advised for
high-risk patients with type B aortic syndrome.
6. Suspected genetic aortic conditions require evaluation at
experienced centres to assess both the patient and their FDRs
for genetic studies. Genetic aortic conditions should be
considered based on family history, syndromic features, age
<60 years, and no CVRFs (guidelines offer a screening
algorithm for thoracic aorta disease). A comprehensive
evaluation of the entire aorta and other vascular territories is
recommended in HTAD. Recent advances in genetics are
enabling personalized and patient-centred assessment. This
includes using different aortic diameter thresholds to indicate
surgery and implementing diverse surveillance algorithms.

4
Gaps in evidence
There are several areas where robust evidence is still lacking and which deserve to be
addressed in future clinical research.
1) Epidemiology and risk factors in PAAD:
a. Improve PAAD risk definition.
b. Provide contemporary data on PAAD prevalence in Europe.
c. Inflammation biomarkers, metabolomics, and proteomics may have prognostic value
in PAAD.
2) Evaluation of peripheral arteries and aorta:
a. Follow-up algorithms can assist PAAD patient management but have limitations and
evidence on cost-effectiveness is needed.
b. The best methodology for aortic measurements remains to be elucidated.
3) Screening for carotid, peripheral arterial, and aortic diseases:
a. Screening in specific populations: research is needed to understand the nuances of
screening in particular populations and whether modifications to current guidelines are
necessary.
b. Patient outcomes and benefits of screening: impact of screening on patient outcome should
be assessed.
4) OMT and PAAD:
a. Research needed on QoL and workability.
b. Research needed for optimal preventive strategies.
c. Exercise therapy and rehabilitation for PAAD should be more accessible and employed.
d. Anti-inflammatory therapy should be investigated.
e. Antithrombotic therapies in specific risk groups of PAAD and patients undergoing
revascularization should be addressed.
5) Aortic aneurysms:
a. Discovering novel individualized risk stratification parameters beyond well-established
markers.
b. Assessing the safety of fluoroquinolone use in patients with aortic aneurysm.
6) Acute aortic syndromes:
a. Assess the management of pregnancy-related AAS.
b. Identify diagnostic biomarkers other than D-dimer.
c. Management in uncomplicated TBAD and IMH should be assessed.
7) Genetic aortic diseases:
a. Need to refine risk estimation in AD, particularly in HTAD, especially the risk of type B aortic
dissection.
b. There is insufficient evidence to support the efficacy of any medication in reducing the risk
of AD.
8) Sex differences in PAAD:
a. Investigate sex and age differences./p>
b. Assess the optimal parameter or indexed parameter to guide intervention decisions in
women with aortic and PAD diseases.

5
Authors and legal information
2024 ESC Guidelines for the management of peripheral arterial and aortic diseases*
Developed by the task force on the management of peripheral arterial and aortic diseases of the
European Society of Cardiology (ESC)
Endorsed by the European Association for Cardio-Thoracic Surgery (EACTS), the European Reference
Network on Rare Multisystemic Vascular Diseases (VASCERN), and the European Society of Vascular
Medicine (ESVM).
Chairpersons
Lucia Mazzolai
Department of Angiology,
Centre Hospitalier Universitaire Vaudois
(CHUV), and Faculty of Biology and Medicine
(FBM), University of Lausanne (UNIL)
Lausanne, Switzerland
Jose F. Rodriguez-Palomares
Cardiovascular Imaging section and Aortic diseases Unit
(VASCERN), Department of Cardiology, Vall d’Hebron Hospital
Universitari, Vall d’Hebron Barcelona Hospital Campus, Vall
d′Hebron Institut de Recerca (VHIR), Barcelona, and Centro de
Investigación Biomédica en Red de Enfermedades Cardiovasculares,
Instituto de Salud Carlos III, Madrid, and Department of Medicine,
Universitat Autònoma de Barcelona, Spain
Task Force Members:
Gisela Teixido-Tura (Task Force Co-ordinator) (Spain), Stefano Lanzi (Task Force Co-ordinator)
(Switzerland), Vinko Boc (Slovenia), Eduardo Bossone (Italy), Marianne Brodmann1 (Austria), Alessandra
Bura-Rivière (France), Julie De Backer2 (Belgium), Sebastien Deglise (Switzerland), Alessandro Della Corte
(Italy), Christian Heiss (United Kingdom), Marta Kałużna-Oleksy (Poland), Donata Kurpas (Poland), Carmel
M. McEniery (United Kingdom), Tristan Mirault (France), Agnes A. Pasquet (Belgium), Alex Pitcher (United
Kingdom), Hannah A.I. Schaubroeck (Belgium), Oliver Schlager (Austria), Per Anton Sirnes (Norway),
Muriel G. Sprynger (Belgium), Eugenio Stabile (Italy), Françoise Steinbach (France), Matthias Thielmann
(Germany), Roland R. J. van Kimmenade (Netherlands), Maarit Venermo (Finland).
1
Representing the European Society of Vascular Medicine (ESVM).
2
Representing the European Reference Network on Rare Multisystemic Vascular Diseases (VASCERN).
ESC subspecialty communities having participated in the development of this document:
Associations: Association for Acute CardioVascular Care (ACVC), Association of Cardiovascular Nursing
& Allied Professions (ACNAP), European Association of Cardiovascular Imaging (EACVI), European
Association of Preventive Cardiology (EAPC), European Association of Percutaneous Cardiovascular
Interventions (EAPCI), Heart Failure Association (HFA).
Councils: Council for Cardiology Practice, Council on Hypertension.
Working Groups: Adult Congenital Heart Disease, Aorta and Peripheral Vascular Diseases, Cardiovascular
Surgery, Thrombosis.
Patient forum
*
Adapted from the 2024 ESC Guidelines for the management of peripheral arterial and aortic diseases
(European Heart Journal; 2024 – doi:10.1093/eurheartj/ehae179) based on uncorrected proofs.

6
Preamble

ESC Classes of recommendations and levels of evidence

Table 1 Classes of recommendations

Definition Wording to use

Class Evidence and/or general agreement that a given Is recommended or

I treatment or procedure is beneficial, useful, is indicated
effective.

Class Conflicting evidence and/or a divergence of opinion about the

II usefulness/efficacy of the given treatment or procedure.

Class Weight of evidence/opinion is in favour of Should be

IIa usefulness/efficacy. considered

Class Usefulness/efficacy is less well established by May be considered

IIb evidence/opinion.

Class Evidence or general agreement that the given Is not

III treatment or procedure is not useful/ effective, and recommended
in some cases may be harmful.

Table 2 Levels of evidence

Level of Data derived from multiple randomized clinical trials or meta-
evidence A analyses.

Level of Data derived from a single randomized clinical trial or large

evidence B non-randomized studies.

Level of Consensus of opinion of the experts and/or small studies,

evidence C retrospective studies, registries.

7
Introduction

The European Society of Cardiology (ESC) has recently completed a

comprehensive review of the existing state of medical evidence and clinical
trial data relating to the management of peripheral arterial and aortic
diseases. Classes of recommendations and levels of evidence have been
evaluated and scored according to the definitions shown in Table
1 and Table 2.

This quick reference booklet summarizes clinical care information

extracted from the full guidelines. The reader is advised that
recommendations with Class of recommendation IIa, Level of Evidence C;
and with Class of recommendation IIb have not been included in the
present document. For greater details, please refer to the published full
guideline available at www.escardio.org/guidelines

Peripheral arterial and aortic diseases (PAAD) are highly prevalent and
significantly increase cardiovascular (CV) mortality and morbidity in the
general population, consequently, intensive preventive strategies are
needed. However, patients with PAAD are generally underdiagnosed and
undertreated compared with patients with coronary artery disease (CAD).
Multidisciplinary approach for effective management is warranted and
early diagnosis is crucial. These guidelines address PAAD, updating and
merging the 2017 peripheral arterial diseases and 2014 aortic diseases
guidelines. The focus is primarily on atherosclerotic arterial diseases, but
they also address some non-atherosclerotic genetic conditions. While not
exhaustive, these 2024 guidelines offer guidance for a holistic,
multidisciplinary approach to PAADs from diagnosis, to surveillance, and
treatment.

8
Epidemiology and risk factors
Main PAAD risk factors are summarized in Figure 1.
Figure 1 Main risk factors associated with atherosclerosis in peripheral
arterial and aortic diseases

PAAD, peripheral arterial and aortic diseases.

9
Evaluation of peripheral arteries and aorta

Overview

To be consistent with existing literature, the term PAD is used to refer to

lower- extremity atherosclerotic arterial disease.

Recommendations for clinical and laboratory, and for

functional and quality of life, assessment in patients
with PAAD
Recommendations Class Level

When managing PAAD, it is recommended to adopt a

comprehensive approach that addresses the entirety of the I B
arterial circulation.

To assess PAAD, it is recommended to perform thorough

I C
clinical, vascular, and CVRFs laboratory evaluation.

Overall evaluation of functional (physical functioning)

performance with objective tests should be considered in IIa B
patients with symptomatic and asymptomatic chronic PAD.

Overall evaluation of self-reported (i.e. by questionnaire)

physical and mental/social HRQoL should be considered in IIa B
patients with PAAD.

CVRFs, cardiovascular risk factor; HRQoL, health-related quality of life;

PAAD, peripheral arterial and aortic diseases; PAD, peripheral arterial
disease.

10
Vascular examination of peripheral arteries
Doppler-measured ankle–brachial index (ABI) is used both at rest or after exercise
for PAD diagnosis and surveillance (Figure 2).

Figure 2 Haemodynamic assessment of PAD

ABI, ankle–brachial index; CLTI, critical limb-threatening ischaemia; PAD,

peripheral arterial disease; TBI, toe– brachial index; TcPO2, transcutaneous
oxygen pressure.

11
 Recommendations for diagnostic tests in patients with PAD
Recommendations Class Level

Measurement of the ABI is recommended as the first-line non-

invasive test for screening and diagnosis of PAD, using I B
an ABI ≤0.90 as a diagnostic criterion.

In the case of non-compressible ankle arteries or ABI >1.40,

additional methods such as TP, TBI or Doppler waveform I B
analysis are recommended.

ABI, ankle–brachial index; PAD, peripheral arterial disease; TBI, toe–

brachial index; TP, toe pressure.

12
Evaluation of the aorta
For reporting purposes, the main anatomical aortic regions are the aortic root,
ascending aorta, aortic arch, descending thoracic aorta (DTA), abdominal aorta
(AA), infrarenal aorta, and the iliac arteries. Additionally, the aorta can also be
subdivided into 11 segments for surgical or endovascular purposes (Figure 3).
Figure 3 Anatomy and aortic segmentsa and upper normal values
for aortic dimensions

a
Numbers represent aortic segments based on the Society for Vascular
Surgery/Society of Thoracic Surgeons (SVS/ STS) classification.

13
In echocardiography, aortic diameters should be measured using the
leading-to- leading edge method during end-diastole in all segments. Given
the high incidence of atherosclerotic plaques/thrombi in the AA, the outer-
to-outer convention should be preferred.

Recommendations for imaging of the aorta

Recommendations Class Level

It is recommended that aortic diameters are measured at

prespecified anatomical landmarks, and the largest diameter of I C
the section be perpendicular to the longitudinal axis.

It is recommended in cases of serial imaging of the aorta over

time to use the same imaging modality with the same I C
measurement method.

It is recommended to consider renal function, pregnancy, age,

and history of allergy to contrast media to select the optimal
I C
imaging modality with minimal radiation exposure and lowest
iatrogenic risk, except for emergency cases.

Indexing aortic diameters to BSA, along with the use of

nomograms, z-scores, or other indexing methods, should be
considered for more accurate assessment of aortic size, IIa B
especially for body sizes at the lower end of the normal
distribution.

BSA, body surface area.

Recommendations for thoracic aortic measurements

Recommendations Class Level

TTE is recommended as the first-line imaging technique in

I B
evaluating thoracic aortic diseases.

It is recommended to report aortic diameters using the leading-

to- leading edge convention in end-diastole by I C
echocardiography.

14
 It is recommended to report aortic diameters using the inner-to-
I C
inner edge convention in end-diastole by CCT or CMR.

It is recommended to report aortic diameters from images

obtained with the double-oblique technique (not axial images) I C
by CCT or CMR.

ECG-triggered CCT is recommended for comprehensive

diagnosis, follow-up, and pre-invasive treatment assessment of I C
the entire aorta, particularly the root and ascending aorta.

CMR is recommended for diagnosis and follow-up of thoracic

I C
aortic diseases, especially when chronic follow-up is required.

CCT, cardiovascular computed tomography; CMR, cardiovascular magnetic

resonance; ECG, electrocardiogram; TTE, transthoracic echocardiography.

Screening for carotid peripheral arterial, and aortic

diseases

Due to the low prevalence of ≥70% asymptomatic carotid artery stenosis

(CS) in the general population (0%–3.1%), widespread screening is not
recommended since it does not reduce stroke risk and might lead to
inappropriate stress and invasive procedures. Conversely, screening for
significant CS in a highly selected population might be cost-effective,
especially if prevalence is ≥20%.

Recommendation for PAD screening

Recommendations Class Level

In patients with diabetes or chronic kidney disease, and normal

IIa B
resting ABI, TBI measurement should be considered.

ABI, ankle–brachial index; TBI, toe–brachial index.

15
 Recommendations for abdominal aortic aneurysm screening
Recommendations Class Level

Screening for AAA with DUS:

Is recommended in men aged ≥65 years with a history of

I A
smoking to reduce the risk of death from ruptured AAA.

Family AAA screening with DUS:

Is recommended for FDRs of patients with AAA aged ≥50,

I C
unless an acquired cause can be clearly identified.

Opportunistic AAA screening with DUS:

Should be considered in symptomatic/

IIa B
asymptomatic PAD patients.

Should be considered in men aged ≥65 years and in women

IIa B
aged ≥75 years during TTE.

AAA, abdominal aortic aneurysm; DUS, duplex ultrasound; PAD, peripheral

arterial disease; TTE, transthoracic echocardiography.

Optimal medical treatment

Optimal medical treatment (OMT), including lifestyle measures and

pharmacological treatment, is recommended for all patients with PAAD.

Recommendations for lifestyle, physical activity, and patient

education
Recommendations Class Level

In patients with PAAD, cessation and abstinence from smoking

of any kind is recommended to reduce the risk of AD, MI, I A
death, and limb ischaemia.

16
 A healthy diet rich in legumes, dietary fibre, nuts, fruits, and
vegetables, with a high flavonoid intake (Mediterranean diet), is
I A
recommended for CV disease prevention in patients
with PAAD.

Low- to moderate-intensity (or high if tolerated)a aerobic

activities are recommended in patients with PAD to increase I A
overall and pain-free walking distance.

In patients with PAAD, behavioural counselling to promote

healthy diet, smoking cessation, and physical activity is I B
recommended to improve the CV risk profile.

It is recommended to promote patient and caregivers' education

and empowerment through tailored guidance on lifestyle I C
adjustments and the importance of regular physical activity.

AD, aortic dissection; CV, cardiovascular; MI, myocardial infarction; PAAD,

peripheral arterial and aortic diseases; PAD, peripheral arterial disease.
a
Low intensity refers to an exercising heart rate of 57%–63% HRmax or a
rate of perceived exertion (RPE) on the Borg’s scale of 9–11. Moderate
intensity refers to an exercising heart rate of 64–76% HRmax or RPE of 12–
13.
Vigorous intensity refers to an exercising heart rate of 77–95% HRmax or
RPE of 14–17.

Recommendations for antihypertensive therapy in patients

with PAAD
Recommendations Class Level

In patients with PAAD and hypertension an SBP target towards

I A
120–129 mmHg, if tolerated, is recommended.

In unilateral RAS patients, it is recommended that

I B
antihypertensive medication include ACEIs/ARBs.

17
 In patients with PAAD and
hypertension, ACEIs or ARBs should be considered as first-line IIa B
antihypertensive therapy.

In RAS-related hypertension, the combination of ACEIs/

ARBs with diuretics and/or calcium channel blockers should be IIa B
considered.

ACEIs, angiotensin-converting enzyme inhibitors; ARBs, angiotensin

receptor blockers; PAAD, peripheral arterial and aortic diseases; RAS, renal
artery stenosis; SBP, systolic blood pressure.

Recommendations for lipid-lowering therapy in patients

with PAAD
Recommendations Class Level

In patients with atherosclerotic PAAD, lipid-lowering therapy is

I A
recommended.

An ultimate LDL-C goal of <1.4 mmol/L (55 mg/dL) and a

>50% reduction in LDL-C vs. baseline are recommended in I A
patients with atherosclerotic PAAD.

Statins are recommended in all patients with PAD. I A

If the target LDL-C level is not achieved on maximally tolerated

statins and ezetimibe, treatment with a PCSK9 inhibitor is
I A
recommended in patients with atherosclerotic PAAD, to achieve
target values.

If the target LDL-C level is not achieved, a combination of

statins and ezetimibe is indicated in patients with I B
atherosclerotic PAAD, to achieve the given target values.

For statin-intolerant patients with atherosclerotic PAAD, at

high CV risk, who do not achieve their LDL-C goal on
I B
ezetimibe, it is recommended to add bempedoic acid either
alone or in combination with a PCSK9 inhibitor.

18
 Statins for the reduction of growth and rupture of AAA should
IIa B
be considered.

Fibrates are not recommended for cholesterol lowering. III B

AAA, abdominal aortic aneurysm; CV, cardiovascular; LDL-C, low-density lipoprotein
cholesterol; PAAD, peripheral arterial and aortic diseases; PCSK9, proprotein convertase
subtilisin/kexin type 9.

Recommendations for the medical management of patients

with PAAD and diabetes
Recommendations Class Level

It is recommended to apply tight glycaemic control (HbA1c <53

mmol/mol [7%]) to reduce microvascular complications in I A
patients with PAAD.

SGLT2i with proven CV benefit are recommended in patients

with T2DM and PAAD to reduce CV events, independent of
I A
baseline or target HbA1c and concomitant glucose-lowering
medication.

GLP-1RAs with proven CV benefit are recommended in

patients with T2DM and PAAD to reduce CV events,
I A
independent of baseline or target HbA1c and concomitant
glucose-lowering medication.

It is recommended to avoid hypoglycaemia in patients

I B
with PAAD.

It is recommended to individualize HbA1c targets according to

I C
comorbidities, diabetes duration, and life expectancy.

It is recommended to prioritize the use of glucose-lowering

agents with proven CV benefits,a,b followed by agents with
I C
proven CV safety,c over agents without proven CV benefit or
safety.

If additional glucose control is needed, metformin should be

IIa B
considered in patients with T2DM and PAAD.

19
CV, cardiovascular; GLP-1RAs, glucagon-like peptide-1 receptor agonists;
HbA1c, glycated haemoglobin; PAAD, peripheral arterial and aortic
diseases; SGLT2i, sodium-glucose co-transporter-2 inhibitors; T2DM, type 2
diabetes mellitus.
a
Empagliflozin, canagliflozin, dapagliflozin, sotagliflozin. bLiraglutide,
semaglutide subcutaneous, dulaglutide, efpeglenatide. cMetformin,
pioglitazone, dipeptidyl peptidase 4 (DPP-4) inhibitor (sitagliptin, alogliptin,
linagliptin), glimepiride, gliclazide, insulin glargine, insulin degludec,
ertugliflozin, lixisenatide, exenatide (extended release), oral semaglutide.

20
Peripheral arterial disease
Lower extremity PAD

PAD syndromes and treatments

Atheromatous lower-extremity PAD is a chronic disease with different clinical

manifestations (see Table 3).

Table 3 PAD categorized according to clinical presentation

PAD, peripheral arterial disease.

21
All patients with PAD are at high risk of MACE, cerebrovascular disease,
and MALE. Prevention of MALE is crucial, and the risk of MACE/MALE
increases with the increased number of arterial beds involved. A
diagnostic PAD algorithm is depicted in Figure 4.
Figure 4 Diagnostic algorithm for PAD

6MWT, six-minute walk test; ABI, ankle–brachial index; AP, ankle pressure;
CLTI, chronic limb-threatening ischaemia; DUS, duplex ultrasound; PAD,
peripheral arterial disease; SPPB, short physical performance battery;
TcPO2, transcutaneous oxygen pressure; TP, toe pressure; WIfI, Wound,
Ischaemia, and foot Infection classification.

22
 Recommendation for diagnostic tests in patients with PAD and
diabetes, renal failure, and wounds
Recommendations Class Level

Measuring TP or TBI is recommended in patients with diabetes

I C
or renal failure if resting ABI is normal.

ABI, ankle–brachial index; TBI, toe–brachial index; TP, toe pressure.

Recommendations for imaging in patients with PAD

Recommendations Class Level

DUS is recommended as the first-line imaging method to

I C
confirm PAD lesions.

In symptomatic patients with aorto-iliac or multisegmental/

complex disease, CTA and/or MRA are recommended as
I C
adjuvant imaging techniques for preparation of revascularization
procedures.

Analysis of anatomical imaging tests in conjunction with

symptoms and haemodynamic tests prior to an invasive I C
procedure is recommended.

CTA, computed tomography angiography; DUS, duplex ultrasound; MRA,

magnetic resonance angiography; PAD, peripheral arterial disease.
Patients with PAD should receive comprehensive OMT(Figure 5 to 9).

23
Figure 5 Optimal medical treatment in patients with PAD

CV, cardiovascular.

24
Figure 6 Treatment algorithm in PAD without wounds

CLTI, chronic limb-threatening ischaemia; PAD, peripheral arterial disease.

25
Figure 7 Treatment algorithm in PAD with wounds

CLTI, chronic limb-threatening ischaemia; PAD, peripheral arterial disease.

26
 Recommendations for exercise therapy in patients with PAD
Recommendations Class Level

In patients with symptomatic PAD, SET is recommended. I A

In those patients undergoing endovascular

I A
revascularization, SET is recommended as an adjuvant therapy.

When SET is not available or feasible, a structured and

monitored (calls, logbooks, connected IIa A
devices) HBET programme should be considered.

Walking should be considered as a first-line training modality.

When walking exercise is not an option, alternative exercise
modes (strength training, arm cranking, cycling, and IIa A
combinations of different training modes) should also be
considered.

Walking training performed at high intensity (77%–95% of

maximal heart rate or 14–17 self-perceived exertion on Borg’s
scale) should be considered to improve walking performance,
IIa A
and high-intensity exercise training (various aerobic training
modes) should be considered to improve cardiorespiratory
fitness.

Training frequency of at least three times per week, training

session duration of at least 30 min, and training programme IIa B
duration of at least 12 weeks should be considered.

HBET, home-based exercise training; PAD, peripheral arterial disease; SET,

supervised exercise training.
In patients with symptomatic PAD, and following endovascular treatment
antithrombotic therapy improves CV prognosis (Figure 8).

27
Figure 8 Long-term antithrombotic therapy in patients with
symptomatic PAD

b.i.d., twice daily; OAC, oral anticoagulant; PAD, peripheral arterial disease;
ASA, aspirin.
a
High risk limb presentation: previous amputation, critical limb threatening
ischaemia, previous revascularization, high-risk comorbidities (heart failure,
diabetes, vascular disease in two or more vascular beds), eGFR <60 mL/
min/1.73m2.

28
Figure 9 Patients with chronic symptomatic PAD after
endovascular revascularization

b.i.d., twice daily; DAPT, dual antiplatelet therapy; OAC, oral anticoagulant;
PAD, peripheral arterial disease; ASA, aspirin; SAPT, single antiplatelet
therapy.
a
High bleeding risk: dialysis or a renal impairment glomerular filtration rate
<15 mL/min/1.73m2, acute coronary syndrome <30 days, history of
intracranial haemorrhage, stroke or TIA, active or clinically signifcant
bleeding.

29
 Recommendations for antithrombotic therapy in patients
with PAD
Recommendations Class Level

Long-term DAPT in patients with PAD is not recommended. III A

Oral anticoagulant monotherapy for PAD (unless for another

III A
indication) is not recommended.

The routine use of ticagrelor in patients with PAD is not

III A
recommended.

It is not recommended to systematically treat patients with

asymptomatic PAD without any sign of clinically III B
relevant ASCVD with antiplatelet drugs.
ASCVD, atherosclerotic cardiovascular disease; DAPT, dual antiplatelet
therapy; PAD, peripheral arterial disease.

Recommendations for interventional treatment of

asymptomatic and symptomatic PAD (general)
Recommendations Class Level

In patients with symptomatic PAD, after a 3-month period

of OMT and exercise therapy, PAD-related QoL assessment is I B
recommended.

It is recommended to adapt the mode and type of

revascularization options to anatomical lesion location, lesion I C
morphology, and general patient condition.

In patients with PAD, revascularization is not recommended if

III B
the reason is to solely prevent progression to CLTI.

In patients with asymptomatic PAD, revascularization is not

III C
recommended.
CLTI, chronic limb-threatening ischaemia; OMT, optimal medical treatment;
PAD, peripheral arterial disease; QoL, quality of life.

30
 Recommendations for interventional treatment of patients with
symptomatic PAD (per arterial bed)
Recommendations Class Level

In femoro-popliteal lesions, drug-eluting treatment should be

IIa A
considered as the first-choice strategy.

In iliac lesions, balloon angioplasty with or without stenting in

external iliac arteries, or primary stenting in common iliac IIa B
arteries, should be considered.

In femoro-popliteal lesions, if revascularization is indicated,

IIa B
endovascular therapy should be considered.

GSV, great saphenous vein.

Recommendation in patients with PAD: follow-up of patients

with PAD
Recommendations Class Level

It is recommended to regularly, at least once a year, follow up

patients with PAD, assessing clinical and functional
I C
status,medication adherence, limb symptoms, and CVRFs,
with DUS assessment as needed.

CVRFs, cardiovascular risk factors; DUS, duplex ultrasound; PAD, peripheral

arterial disease.

31
Chronic limb threatening ischaemia

Recommendations for the management of CLTI

Recommendations Class Level

For limb salvage in patients with CLTI, revascularization is

I B
recommended.

Early recognition of CLTI and referral to the vascular team are

I C
recommended for limb salvage.

CLTI, chronic limb-threatening ischaemia.

Recommendations for medical treatment in patients with CLTI

Recommendations Class Level

It is recommended that patients with CLTI be managed by a

I C
vascular team.

In patients with CLTI and ulcers, offloading mechanical tissue

I C
stress is recommended to allow wound healing.

It is recommended to treat infection with antibiotics. I C

Lower-limb exercise training is not recommended in patients

III C
with CLTI and wounds.

CLTI, chronic limb-threatening ischaemia.

32
 Recommendations for interventional treatment of CLTI
Recommendations Class Level

In CLTI patients, it is recommended to perform

I B
revascularization as soon as possible.

In CLTI, it is recommended to use autologous veins as the

I B
preferred conduit for infra-inguinal bypass surgery.

In multilevel vascular disease, it is recommended to eliminate

I C
inflow obstructions when treating downstream lesions.

An individual risk assessment (weighing the patient’s individual

procedural risk of endovascular vs. surgical revascularization) I C
by a multidisciplinary vascular team is recommended.

CLTI, chronic limb-threatening ischaemia.

Recommendations for follow-up in patients with CLTI

Recommendations Class Level

In patients with CLTI, following revascularization it is

I C
recommended to follow up patients on a regular basis.

At follow-up, it is recommended to assess clinical,

haemodynamic and functional status, limb symptoms, treatment I C
adherence, and CVRFs.

CLTI, chronic limb-threatening ischaemia; CVRFs, cardiovascular risk

factors.

Acute limb ischaemia

ALI is a medical emergency and timely recognition is crucial to successful

treatment. Patients should be rapidly evaluated by a vascular specialist or
rapidly transferred to a facility with such resources Figure 10.

33
Figure 10 Management of acute limb ischaemia

ALI, acute limb ischaemia; CTA, computed tomography angiography; DSA, digital
subtraction angiography; DUS, duplex ultrasound; MRA, magnetic resonance
angiography.
Should not delay treatment
a

34
 Recommendations for the management of patients presenting
with ALI
Recommendations Class Level

In patients with ALI, it is recommended that an urgent

evaluation is performed by a vascular clinician with sufficient
I C
experience to assess limb viability and implement appropriate
therapy.

In cases of neurological deficit, urgent revascularization is

recommended; diagnostic imaging is recommended to guide
I C
treatment, provided it does not delay treatment, or if the need
for primary amputation is obvious.

In the absence of severe neurological deficit, revascularization

is recommended within hours of initial imaging in a case-by- I C
case decision.

Treatment with analgesics is recommended as soon as possible

I C
for pain control.

It is recommended to monitor for compartment syndrome after

I C
revascularization and treat (fasciotomy).

It is recommended to assess clinical and haemodynamic success

I C
following revascularization.

In patients with ALI, it is recommended to obtain a

comprehensive medical history and determine the cause of I C
thrombosis and/or embolization.

ALI, acute limb ischaemia.

35
Extracranial carotid and vertebral artery disease

Overview

Atherosclerotic CS is defined as ≥50% narrowing of the extracranial internal

carotid artery (ICA), with stenosis severity estimated using the North
American Symptomatic Carotid Endarterectomy Trial (NASCET) method or
its non-invasive equivalent assessed by DUS (Figure 11).
Figure 11 North American Symptomatic Carotid Endarterectomy Trial/
European Carotid Surgery Trial methods

ECST, European Carotid Surgery Trial; NASCET, North American Symptomatic Carotid
Endarterectomy trial.
Carotid DUS is safe, accurate, and reliable if performed by a skilled vascular specialist. It
is the first-line imaging modality for screening, diagnosis, and surveillance of
extracranial carotid arteries. The degree of stenosis is mostly based on Doppler
analysis of blood flow in the common carotid artery (CCA), ICA, and external carotid
artery (Table 4). Vertebral and subclavian arteries must also be checked. In some cases,
indirect signs of severe stenosis have to be evaluated by transcranial and/or ophthalmic
artery Doppler. Severe arterial calcification can decrease DUS accuracy.

36
 Table 4 Peak systolic velocity criteria for grading internal
carotid artery stenosis
50%–69% (moderate
% stenosis ≥70% (severe stenosis)
stenosis)

PSV threshold 125–230 cm/s >230 cm/s

------------------------- -------------------------
≥180 cm/s Overestimation with SRUCC criteria
or but no consensus
≥125 cm/s + PSV ICA/
CCA ≥2

CCA, common carotid artery; ICA, internal carotid artery; PSV, peak systolic
velocity; SRUCC, Society of Radiologists in Ultrasound.

Recommendations for carotid artery stenosis assessment

Recommendations Class Level

It is recommended to use the NASCET method or its non-

I B
invasive equivalent to assess ICA stenosis.

It is recommended to use DUS as first-line imaging to

I C
diagnose ICA stenosis.

It is not recommended to use the ECST method for ICA stenosis

III C
assessment.

DUS, duplex ultrasound; ECST, European Carotid Surgery Trial; ICA, internal
carotid artery; NASCET, North American Symptomatic Carotid
Endarterectomy Trial.

37
Asymptomatic carotid artery stenosis

Recommendation for medical treatment in patients with

asymptomatic CAS
Recommendations Class Level

In patients with symptomatic CS, not undergoing carotid

endarterectomy or stenting, DAPT with low-dose aspirin and
clopidogrel (75 mg) is recommended for the first 21 days or I A
longer, followed by clopidogrel 75 mg or long-term aspirin to
reduce the risk of stroke.
CS, carotid artery stenosis; DAPT, dual antiplatelet therapy.
For invasive treatment of asymptomatic CAS, the overall risk reduction is low compared
with OMT. However, there is a need to target revascularization in a subgroup of patients
with clinical and/or imaging features that increase the risk for stroke on OMT (Table 5).

Table 5 High-risk features associated with increased risk of stroke in

patients with asymptomatic internal CAS on optimal medical treatment

Clinicala Contralateral TIA/stroke

Cerebral imaging Ipsilateral silent infarction

Stenosis progression (>20%)

Spontaneous embolization on transcranial Doppler
(HITS)
Impaired cerebral vascular reserve
Ultrasound/ CT imaging
Large plaques
Echolucent plaques
Increased juxta-luminal black (hypoechogenic)
area

Intraplaque haemorrhage
MRAb
Lipid-rich necrotic core
CT, computed tomography; HITS, high-intensity transient signal; MRA, magnetic
resonance angiography; TIA, transient ischaemic attack.
a
Age is not a predictor of poorer outcome. bMore than 40 mm2 on digital analysis.

38
The general algorithm of CAS management is presented in Figure 12.

Recommendations for interventional treatment in patients with

asymptomatic CAS
Recommendations Class Level

When ICA revascularization is considered, documented peri-

operative stroke/death rates should be <3% and the patient’s life
IIa B
expectancy should be considered >5 years after careful
consideration of the risks and benefits by a vascular team.

In ‘average surgical risk’ patients over 75 years of age with

a CS of 60%–99%, in the presence of high-risk features, CEA, IIa B
in addition to OMT, should be considered.

In asymptomatic patients with ICA stenosis, in the absence of

high-risk features and with a life expectancy <5 years, routine III A
revascularization is not recommended.

CEA, carotid endarterectomy; CS, carotid artery stenosis; ICA, internal

carotid artery; OMT, optimal medical treatment.

39
Figure 12 Algorithm of carotid artery stenosis management

40
CAS, carotid artery stenting; CEA, carotid endarterectomy; CTA, computed
tomography angiography; MRA, magnetic resonance angiography; OMT,
optimal medical treatment; TCAR, transcarotid artery revascularization; TIA,
transient ischaemic attack.
a
Assess presence of high-risk features according to Table 5. If surgery is
considered, assess the overall risk related to surgery.

Symptomatic carotid artery stenosis

Recommendations for evaluation and medical treatment in

patients with symptomatic CAS
Recommendations Class Level

DAPT is recommended in the early phase of minor strokes in

patients with ICA stenosis, if not revascularized, for at least 21 I A
days, considering the bleeding risk.

It is recommended that symptomatic ICA stenosis patients are

I C
assessed by a vascular team including a neurologist.

DAPT, dual antiplatelet therapy (aspirin and clopidogrel); ICA, internal

carotid artery.

Recommendations for interventions in patients with

symptomatic CAS
Recommendations Class Level

It is recommended to perform CEA of symptomatic 70%–

99% ICA stenosis provided a documented 30-day risk of I A
procedural death/ stroke is <6%.

If indicated, it is recommended to perform CEA within 14 days

I B
in symptomatic ICA stenosis patients.

41
 OMT is recommended for all symptomatic ICA stenosis
I A
patients.

CEA of symptomatic 50%–69% ICA stenosis should be

considered provided a documented 30-day risk of procedural IIa A
death/stroke is <6%.

For symptomatic patients at high risk for CEA with a 70%–

99% ICA stenosis, CAS should be considered provided a IIa B
documented 30-day risk of procedural death/stroke is <6%.

Revascularization is not recommended in patients

III A
with ICA lesions <50%.

CEA, carotid endarterectomy; ICA, internal carotid artery; OMT, optimal

medical treatment.

Recommendations for follow-up in patients with CAS

Recommendations Class Level

Once-yearly follow-up is recommended to check

I A
for CVRFs and treatment compliance.

After ICA stent implantation, DAPT with aspirin and

I A
clopidogrel is recommended for at least 1 month.

After ICA revascularization, long-term aspirin or clopidogrel is

I B
recommended.

During follow-up, it is recommended to assess neurological

symptoms, CVRFs, and treatment adherence at least yearly in I C
patients with CS.

After ICA revascularization, surveillance with DUS is

I C
recommended within the first month.

CS, carotid artery stenosis; CVRFs, cardiovascular risk factors; DAPT, dual
antiplatelet therapy; DUS, duplex ultrasound; ICA, internal carotid artery.

42
Other arterial locations

Subclavian artery disease

Atherosclerotic upper-limb artery disease (UEAD) is most frequently

located in the subclavian artery. Isolated subclavian stenosis (SS) is often
asymptomatic and may be suspected because of an absolute inter-
arm SBP difference >10–15 mmHg.

Recommendations for the management of subclavian artery

stenosis
Recommendations Class Level

Bilateral arm BP measurement is recommended for all patients

I B
with PAAD.

In symptomatic patients with atherosclerotic subclavian artery

disease (TIA/stroke, coronary subclavian steal syndrome,
ipsilateral haemodialysis access dysfunction, severe ischaemia),
IIa B
both revascularization options (endovascular ± stenting or
surgery) should be considered and discussed case by case by a
vascular team.

In patients with atherosclerotic subclavian artery disease,

revascularization:

Routine revascularization in patients with atherosclerotic

III C
subclavian artery disease is not recommended.

BP, blood pressure; PAAD, peripheral arterial and aortic diseases; TIA,
transient ischaemic attack.

43
Renal artery disease

Table 6 Clinical signs suggestive of renal artery disease

Hypertension onset before 30 years of age

Severe hypertension after the age of 55 years, when associated with CKD or
heart failure

Hypertension and abdominal bruit

Rapid and persistent worsening of previously controlled hypertension

Resistant hypertension
Three antihypertensive drugs including a diuretic agent, OR
≥4 antihypertensive drugs, AND
Other secondary form unlikely

Hypertensive crisis (i.e. acute renal failure, acute heart failure, hypertensive
encephalopathy, or grade 3–4 retinopathy)

New azotaemia or worsening of renal function after treatment

with RAAS blockers

Unexplained atrophic kidney or discrepancy in kidney size, or unexplained renal

failure

Flash pulmonary oedema

CKD, chronic kidney disease; RAAS, renin–angiotensin–aldosterone

system.

44
Figure 13 Diagnostic and treatment algorithm for RAS

45
CTA, computed tomography angiography; MRA, magnetic resonance
angiography; OMT, optimal medical treatment; Pd/Pa, distal coronary
pressure to aortic pressure ratio; PSV, peak systolic velocity; RAR, renal-
aortic peak flow velocity ratio; RAS, renal artery stenosis.

a
Kidney viability in RAS

Signs of viability Signs of non-viability

Renal size >8 cm <7 cm

Renal cortex Distinct cortex (>0.5 cm) Loss of corticomedullar

differentiation

Proteinuria Albumin-creatinine ratio Albumin-creatinine ratio >30

<20 mg/mmol mg/mmol

Renal resistance <0.8 >0.8

index
b
Rapidly progressive, treatment-resistant arterial hypertension; rapidly
declining renal function; flash pulmonary oedema; solitary kidney.
c
Resting mean pressure gradient >10 mmHg; systolic hyperaemic pressure
gradient >20 mmHg; renal PdPa ≤ 0.9 (or 0.8).

Recommendations for diagnostic strategies for RAS

Recommendations Class Level

In patients with atherosclerotic RAS, it is recommended to

assess clinical high-risk features and kidney viability when I B
evaluating renal artery revascularization.

DUS is recommended as the first-line imaging modality in

I B
patients with suspicion of RAS

RAS, renal artery stenosis.

46
 Recommendations for treatment strategies for RAS
Recommendations Class Level

Revascularization

In patients with atherosclerotic unilateral >70% RAS,

concomitant high-risk features, and signs of kidney viability, IIa B
renal artery revascularization should be considered.

In patients with atherosclerotic bilateral (>70%) RAS or RAS in

a solitary kidney, renal artery revascularization should be IIa B
considered.

In patients with hypertension and/or signs of renal dysfunction

due to RAS caused by fibromuscular dysplasia,
IIa B
revascularization with balloon primary angioplasty and bailout
stenting should be considered.

In patients with an indication for renal artery revascularization

and complex anatomy, or after failed endovascular
IIa B
revascularization, open surgical revascularization should be
considered.

In patients with atherosclerotic unilateral RAS, routine

III A
revascularization is not recommended.

RAS, renal artery stenosis.

Visceral artery disease

Occlusive chronic mesenteric ischaemia is mostly caused by

atherosclerosis and more frequently affects females (65%–72%). (Figure
14).

47
Figure 14 Algorithm of chronic mesenteric ischaemia
management

CA, coeliac artery; CMI, chronic mesenteric ischaemia; CTA, computed

tomography angiography; MALS, median arcuate ligament syndrome;
NOMI, non-occlusive mesenteric ischaemia; SMA, superior mesenteric
artery.

48
Recommendations in patients with visceral artery stenosis
Recommendations Class Level

In patients with acute mesenteric ischaemia due to acute

occlusion of the SMA, endovascular revascularization is I B
recommended.

In patients with suspected acute or chronic mesenteric

I C
ischaemia, CTA is recommended.

In patients with acute or chronic mesenteric ischaemia,

I C
assessment by a vascular team is recommended.

Revascularization of asymptomatic atherosclerotic visceral

III C
artery stenosis is not recommended.

CTA, computed tomography angiography; SMA, superior mesenteric artery.

49
Aorta

Atheromatous disease of the aorta

Atherosclerotic plaque classification is based on plaque thickness and the

presence of ulceration or mobile components.

Recommendations for primary and secondary prevention in

aortic atheromatous plaques
Recommendations Class Level

Primary prevention

Anticoagulation or DAPT are not recommended in aortic

III C
plaques since they present no benefit and increase bleeding risk.

Secondary prevention after an embolic event related to aortic

atherosclerosis

In patients with an embolic event and evidence of an aortic arch

atheroma, intensive lipid management to an LDL-C target <1.4 I A
mmol/L (<55 mg/dL) is recommended to prevent recurrences.

In patients with an embolic event and evidence of an aortic arch

I C
atheroma, SAPT is recommended to prevent recurrences.

DAPT, dual antiplatelet therapy; LDL-C, low-density lipoprotein cholesterol;

SAPT, single antiplatelet therapy.

50
Aortic aneurysms

General concepts

Based on location, aortic aneurysms are classified into TAA and abdominal
aortic aneurysm (AAA).

Recommendations for initial evaluation of thoracic aortic

aneurysm and abdominal aortic aneurysm
Recommendations Class Level

When an aortic aneurysm is identified at any location,

assessment of the entire aorta is recommended at baseline and I C
during follow-up.

When a TAA is identified, assessment of the aortic valve

I C
(especially for BAV) is recommended.

BAV, bicuspid aortic valve; TAA, thoracic aortic aneurysm.

Thoracic aortic aneurysms

TAAs can involve different parts of the DTA and may extend to the
AA: TAAA. For untreated DTA aneurysm patients, 5-year survival is about
54%, with aortic rupture as the leading cause of death. Figure 15 proposes
a follow-up algorithm for patients with TAA. In cases of aortic root or
proximal ascending aorta dilatation, after initial diagnosis by TTE the basal
diameter and extension must be confirmed by CMR or CCT.

51
Recommendation for the surveillance of patients with thoracic
aortic aneurysms (non-heritable thoracic aortic disease)
Recommendations Class Level

In thoracic aortic dilatation, TTE is recommended at diagnosis

to assess aortic valve anatomy and function, aortic root, and
I C
ascending aorta diameters. Additionally, a global aortic
evaluation using all echocardiographic views is recommended.

CMR or CCT is recommended for surveillance of patients with

aneurysm at the distal ascending aorta, aortic arch, DTA, I C
or TAAA.

In thoracic aortic dilatation, CCT or CMR is recommended to

confirm TTE measurements, rule out aortic asymmetry, and I C
determine baseline diameters for follow-up.

TTE is not recommended for the surveillance of aneurysms in

III C
the distal ascending aorta, aortic arch, or DTA.

CCT, cardiac computed tomography; CMR, cardiovascular magnetic

resonance; DTA, descending thoracic aorta; TAAA, thoraco-abdominal
aortic aneurysm; TTE, transthoracic echocardiography.

52
Figure 15 Surveillance of patients with non-heritable thoracic
aortic disease and AAA

53
AAA, abdominal aortic aneurysm, BAV, bicuspid aortic valve; CCT,
cardiovascular computed tomography; HTAD, heritable thoracic aortic
disease; CMR, cardiovascular magnetic resonance; TAV, tricuspid aortic
valve; TTE, transthoracic echocardiography.
a
36–44 mm in women. bFor TAV and BAV: age <50 years; height <1.69m;
ascending length >11cm; uncontrolled hypertension; and, for BAV:
coarctation; family history of acute aortic events.

Abdominal aortic aneurysms

An AAA is defined as a focal dilation generally ≥30 mm. Most AAAs are
fusiform, and many are lined with laminated thrombi. Their prevalence
increases with age, with a 4:1 male/female ratio.

Recommendations for surveillance of patients with AAA

Recommendations Class Level

DUS surveillance is recommended every 6 months in men

with AAA of 50–55 mm and in women with AAA of 45–50 I B
mm.

CCT or CMR is recommended if DUS does not allow adequate

I B
measurement of AAA diameter.

DUS is recommended for AAA surveillance. I C

DUS surveillance every 3 years should be considered in patients

IIa B
with AAA of 30–<40 mm.

DUS surveillance should be considered annually in women

with AAA of 40–<45 mm and in men with AAA of 40–<50 IIa B
mm.

AAA, abdominal aortic aneurysm; CCT, cardiac computed tomography;

CMR, cardiovascular magnetic resonance; DUS, duplex ultrasound.

54
Optimal medical treatment of aortic aneurysms

Recommendation for medical treatment in patients

with TAA or AAA
Recommendations Class Level

In patients with aortic aneurysm (TAA and/or AAA), optimal

implementation of CV risk management and medical treatment I C
are recommended to reduce MACE.

AAA, abdominal aortic aneurysm; CV, cardiovascular; MACE, major adverse

cardiovascular events; TAA, thoracic aortic aneurysm.

Surgical management of aortic aneurysms

Recommendations for surgery in aortic root and ascending

aorta dilatation associated with tricuspid aortic valve
Recommendations Class Level

Surgery is recommended in patients with dilatation of the aortic

root or ascending aorta with a tricuspid aortic valve and a I B
maximum diameter of ≥55 mm.

Valve-sparing aortic root replacement is recommended in

patients with aortic root dilatation if performed in experienced I B
centres and durable results are expected.

VKAs are recommended lifelong for all patients with a Bentall

I B
procedure with an MHV prosthesis.

In patients with dilatation of the tubular ascending aorta who

can be offered surgery with low predicted risk,a ascending aortic
IIa B
replacement should be considered at a maximum diameter >52
mm.

55
 In patients undergoing surgery for tricuspid aortic valve disease
who have concomitant dilatation of the aortic root or ascending
tubular aorta, and low predicted surgical risk, ascending aorta or IIa B
root replacement should be considered at a maximum diameter
≥45 mm, otherwise ≥50 mm.

MHV, mechanical heart valve; VKA, vitamin K antagonist. aIndividual

patient’s risk <3%.

Recommendations for surgery in aortic arch aneurysms

Recommendations Class Level

In patients with low or intermediate operative risk with an aortic

arch aneurysm and recurrent episodes of chest pain not
I C
attributable to non-aortic causes, open surgical replacement of
the arch is recommended.

In patients with an isolated aortic arch aneurysm who are

asymptomatic and have low operative risk, open surgical
IIa B
replacement should be considered at an arch diameter of ≥55
mm.

Recommendations for the management of patients presenting

with descending thoracic aortic and thoraco-abdominal aortic
aneurysms
Recommendations Class Level

In patients with unruptured DTA aneurysm (without HTAD),

I B
elective repair is recommended if diameter ≥55 mm.

In patients without HTAD with unruptured DTA aneurysm,

when elective repair is indicated and anatomy is I B
suitable, TEVAR is recommended over open repair.

56
 In patients with DTA aneurysm who undergo TEVAR with
planned LSA coverage, it is recommended to revascularize I B
the LSA before TEVAR to reduce the risk of SCI and stroke.

In patients with unruptured degenerative TAAA, elective repair

I B
is recommended when the diameter is ≥60 mm.

In patients without significant comorbidities and with

unruptured DTA aneurysm, when elective repair is indicated
IIa B
and anatomy is unsuitable for TEVAR, open repair should be
considered if life expectancy exceeds 2 years.

In TAAA, surgical repair should be considered at diameters ≥55

mm if patients present with high-risk features, are at very low
IIa B
risk, and are under the care of experienced surgeons in a
multidisciplinary aorta team.

In patients with unruptured degenerative TAAA and suitable

anatomy, when elective repair is indicated, endovascular repair
IIa B
using fenestrated and/or branched endografts should be
considered in experienced centres.

DTA, descending thoracic aorta; HTAD, heritable thoracic aortic disease;

LSA, left subclavian artery; SCI, spinal cord ischaemia; TAAA, thoraco-
abdominal aortic aneurysm; TEVAR, thoracic endovascular aortic aneurysm
repair.
For heritable thoracic aortic disease refer to Section 10 of the full
guidelines.
The individual decision-making process in AAA patients is displayed
in Figure 16.

57
Figure 16 Algorithm for individual decision-making process in the
treatment of patients with abdominal aortic aneurysm

AAA, abdominal aortic aneurysm; EVAR, endovascular aortic aneurysm repair.

58
Recommendations for the management of patients presenting
with AAA
Recommendations Class Level

Elective repair is recommended if AAA diameter is ≥55 mm in

I A
men or ≥50 mm in women.

In ruptured AAA with suitable anatomy, endovascular repair is

recommended over open repair to reduce peri-operative I B
morbidity and mortality.

Prior to AAA repair, DUS assessment of the femoro-popliteal

segment, to detect concomitant aneurysms, should be IIa B
considered.

In patients with AAA with suitable anatomy and reasonable life

expectancy (>2 years), EVAR should be considered as the IIa B
preferred therapy, based on shared decision-making.

In patients with AAA and limited life expectancy (<2 years),

III B
elective AAA repair is not recommended.

Prior to AAA repair, routine evaluation with coronary

angiography and systematic revascularization in patients with III C
chronic coronary syndromes is not recommended.

AAA, abdominal aortic aneurysm; DUS, duplex ultrasound; EVAR,

endovascular aortic aneurysm repair.

59
Endoleaks

Endoleaks are defined as the persistence of blood flow outside the graft
but inside the aneurysm sac, preventing thrombosis.

Recommendations for the management of patients presenting

with endoleaks
Recommendations Class Level

It is recommended to perform 30-day imaging after TEVAR/

EVAR, by CCT and DUS/CEUS, to assess the success of I B
intervention.

It is recommended to re-intervene to achieve a seal in patients

I B
with type I endoleak after TEVAR/EVAR.

It is recommended to re-intervene, principally by endovascular

means, to achieve a seal in patients with type III endoleak I B
after TEVAR/EVAR.

CCT, cardiovascular computed tomography; CEUS, contrast-enhanced

ultrasound; DUS, Doppler ultrasound; TEVAR/EVAR, thoracic endovascular
aortic aneurysm repair.

Long term follow up after aortic repair

Long-term success in the management of aortic aneurysms depends also

on strict post-treatment surveillance, for both secondary prevention of the
aortic disease and early identification of post-repair complications.

60
Recommendations for follow-up after treatment of aortic
aneurysms
Recommendations Class Level

Thoracic aortic aneurysm

After open repair of TAA, an early CCT is recommended within

1 month, and then yearly CCT follow-up for the first 2 post-
I B
operative years and every 5 years thereafter is recommended if
findings are stablea.

After TEVAR, follow-up imaging is recommended at 1 and 12

months post-operatively, then yearly until the fifth post- I B
operative year if no abnormalitiesb are documented.

After 5 post-operative years without complications, continuing

long-term follow-up of TEVAR by CCT every 5 years should IIa B
be considered.

Abdominal aortic aneurysm

After open repair of AAA, first follow-up imaging is

recommended within 1 post-operative year, and every 5 years I A
thereafter if findings are stable.

After EVAR, follow-up imaging is recommended with CCT (or

CMR) and DUS/CEUS at 1 month and 12 months post-
operatively, then, if no abnormalitiesb are documented, DUS/
I A
CEUS is recommended every year,
repeating CCT or CMR (based on potential artefacts) every 5
years.

In higher-risk patients, i.e. with inadequate sealing or type II

endoleak at first CCT control, more frequent DUS/ IIa B
CEUS imaging should be consideredc.

In low-riskd patients, from 1 year post-operatively after EVAR,

IIa B
repeating DUS/CEUS every 2 years should be considered.

61
 If any abnormality during DUS/CEUS is found, confirmation
should be considered using additional CCT or CMR (based on IIa B
potential artefacts).

AAA, abdominal aortic aneurysm; CCT, cardiovascular computed

tomography; CEUS, contrast-enhanced ultrasound; CMR, cardiovascular
magnetic resonance; DUS, Doppler ultrasound; EVAR, endovascular aortic
repair; OMT, optimal medical treatment; TAA, thoracic aortic aneurysm;
TEVAR, thoracic endovascular aortic repair.
a
Both at the level of the treated segment and in the residual native
aorta. bIncluding: endoleak (any type), enlargement of the excluded
aneurysm, and stent graft migration/separation/fracture. ce.g. imaging
every 6 months during the first year, thereafter every 2–3 years. dLow-risk:
early sac shrinkage >10 mm, relatively younger age (<70 years), proximal
and distal sealing >10 mm, no endoleak.

Acute thoracic aortic syndromes

General concepts

AAS are life-threatening emergencies, to guide AAS management, several

anatomical classifications have been developed, such as the Stanford and
the DeBakey systems (Figure 17).
Recently, a European update of the Stanford classification—Type Entry
Malperfusion (TEM) classification—has been proposed. Furthermore, if
time elapsed from symptom onset to diagnosis is considered, AAS can be
divided into hyperacute (<24 h), acute (1–14 days), subacute (15–90 days),
and chronic (>90 days) (Figure 17).
Early diagnosis is still a major pitfall in managing AAD patients, therefore, a
diagnostic multiparametric algorithm is proposed (Figure 18).

62
Figure 17 Anatomical and temporal classification of AAS

AAS, acute aortic syndrome.

63
Figure 18 Multiparametric diagnostic work-up of AAS

AAS, acute aortic syndrome; ADD-RS, aorta dissection detection-risk score;

CCT, cardiovascular computed tomography; CXR, chest X-ray; ECG,
electrocardiogram; POCUS, point-of-care ultrasound; STEMI, ST elevation
myocardial infarction; TOE, transoesophageal echocardiography; TTE,
transthoracic echocardiography.
+: findings compatible with AAS. Consider STEMI as part of AAS. aIn
haemodynamically unstable patients: consider TTE and/or TOE as first-line
imaging technique depending on local expertise and availability.

64
AAS care should be centralized in experienced centres and managed by
aorta teams. The cornerstone in AAS is initial reduction of the SBP below
120 mmHg and heart rhythm ≤60 beats per minute (bpm). The aim is to
decrease aortic wall stress to avoid further extension of dissection with
possible rupture or malperfusion. Adequate pain control is necessary and
intravenous morphine can be cautiously titrated.
Recommendations for medical treatment in AAS
Recommendations Class Level

In patients with AAS, immediate anti-impulse treatment

targeting SBP <120 mmHg and heart rate ≤60 bpm is
I B
recommended. In cases of spinal ischaemia or concomitant
brain injury, maintaining higher MAP is recommended.

Intravenous BBs (e.g. labetalol or esmolol) are recommended as

first-line agents. If necessary, i.v. vasodilators (e.g. I B
dihydropyridine calcium blockers or nitrates) could be added.

Invasive monitoring with an arterial line and continuous three-

lead ECG recording, as well as admission to an intensive care I B
unit, is recommended.

In patients with AAS who can be managed conservatively and

who achieved haemodynamic targets with i.v. anti-impulse
therapy, switching to oral BBs and, if necessary, up-titration of I B
other BP- lowering agents, is recommended after 24 hours if
gastrointestinal transit is preserved.

Adequate pain control to achieve haemodynamic targets is

I C
recommended.

If the patient has a contraindication for BBs, a non-

IIa B
dihydropyridine calcium blocker should be considered.
AAS, acute aortic syndrome; BB, beta-blocker; bpm, beats per minute; ECG,
electrocardiogram; i.v., intravenous; MAP, mean arterial pressure; SBP,
systolic blood pressure.

65
Interventional treatment in acute TAAD and acute TBAD is described in the
next sections and summarized in Figure 19.
Figure 19 Interventional treatment algorithm in AAD

66
AAD, acute aortic dissection; Ao, aorta; CCT, cardiovascular computed
tomography; OMT, optimal medical treatment; TEVAR, thoracic
endovascular aortic repair.
a
On serial imaging in the acute phase during the hospital stay. bOngoing
hypertension despite more than three classes of antihypertensive
drugs. cDefined as the presence of adequate proximal and distal landing
zones for the prosthesis and adequate iliac/femoral vessels for vascular
access. dBetween 14 and 90 days after dissection onset.

Recommendations for intervention in type A acute aortic

dissection
Recommendations Class Level

In patients with acute TAAD, emergency surgical consultation

and evaluation and immediate surgical intervention is I B
recommended.

In patients with acute TAAD who have extensive destruction of

the aortic root, a root aneurysm, or a known genetic aortic
I B
disorder, aortic root replacement is recommended with a
mechanical or biological valved conduit.

In patients presenting with acute TAAD, transfer from a low- to

a high-volume aortic centre with the presence of a
multidisciplinary team should be considered to improve survival IIa B
if transfer can be accomplished without significant delay in
surgery.

TAAD, type A aortic dissection.

67
 Recommendations for aortic repair strategies in type A acute
aortic dissection
Recommendations Class Level

In patients with acute TAAD and a partially dissected aortic root

but no significant aortic valve leaflet pathology, aortic valve I B
resuspension is recommended over valve replacement.

In patients with acute TAAD undergoing aortic repair, an open

distal anastomosis is recommended to improve survival and I B
increase FL thrombosis rates.

In patients with acute TAAD without an intimal tear in the arch

or a significant arch aneurysm, hemi-arch repair is I B
recommended over more extensive arch replacement.

FL, false lumen; TAAD, type A aortic dissection.

In acute TAAD with malperfusion, operative mortality correlates with the

number of affected organs. Around 30% of patients develop malperfusion
syndrome, necessitating surgical and hybrid interventions for affected
patients.

Recommendations for the management of malperfusion in the

setting of acute aortic dissection
Recommendations Class Level

In patients with acute TAAD presenting with malperfusion

(cerebral, mesenteric, lower limb, or renal), immediate aortic I B
surgery is recommended.

In patients with acute TAAD presenting with cerebral

malperfusion or non-haemorrhagic stroke, immediate aortic
IIa B
surgery should be considered to improve neurological outcome
and reduce mortality.

TAAD, type A aortic dissection.

68
 Recommendations for the management of patients presenting with
acute type B aortic dissection
Recommendations Class Level

Medical therapy including pain relief and blood pressure control is

I B
recommended in all patients with acute TBAD.

In patients with complicated acute TBAD, emergency intervention

I B
is recommended.

In patients with complicated acute TBAD, TEVAR is

I B
recommended as the first-line therapya.

In patients with acute TBAD, BBs should be considered as the first-

IIa B
line medical therapy.

In patients with uncomplicated acute TBAD, TEVAR in the

subacute phase (between 14 and 90 days) should be considered in
IIa B
selected patients with high-risk features to prevent aortic
complications.
BBs, beta-blockers; HTAD, heritable thoracic aortic disease; TBAD, type B aortic
dissection; TEVAR, thoracic endovascular aortic repair.
See also Figure 19. aExcept in patients with known or suspected HTAD.

Recommendations for the management of patients presenting with

chronic type B aortic dissection
Recommendations Class Level

Antihypertensive therapy is recommended in all patients with

I B
chronic TBAD.

In chronic TBAD with acute symptoms of malperfusion, rupture, or

I C
progression of disease, emergency intervention is recommended.

In patients with chronic TBAD and a descending thoracic aortic

diameter ≥60 mm, treatment is recommended in patients at I B
reasonable surgical risk.
TBAD, type B aortic dissection.

69
Intramural haematoma

Most cases (60%–70%) involve the DTA (ascending aorta ~30%, aortic arch
~10%).

Recommendations for the management of intramural

haematoma
Recommendations Class Level

In patients with IMH, medical therapy including pain relief and

I C
blood pressure control is recommended.

In type A IMH, urgent surgery is recommended. I C

In type B IMH, initial medical therapy under careful

I C
surveillance is recommended.

In uncomplicateda type B IMH, repetitive imaging (CCT or

I C
CMR) is indicated.

In complicateda type B IMH, TEVAR is recommended. I C

CCT, cardiovascular computed tomography; CMR, cardiovascular magnetic

resonance; IMH, intramural haematoma; TEVAR, thoracic endovascular
aortic repair.
a
Uncomplicated/complicated IMH refers to the absence or presence of
recurrent pain, expansion of the IMH, periaortic haematoma, and intimal
disruption.

70
Penetrating atherosclerotic ulcer

Surgery is recommended in type A PAU with the option of a ‘wait-and-see

strategy’ in highly selected high-risk patients with no high-risk features.
However, in uncomplicated type B PAU, medical treatment along with
careful clinical and imaging surveillance is recommended.

Recommendations for the management of PAU

Recommendations Class Level

In all patients with PAU, medical therapy including pain relief

I C
and blood pressure control is recommended.

In cases of type A PAU, surgery is recommended. I C

In cases of type B PAU, initial medical therapy under careful

I C
surveillance is recommended.

In uncomplicated type B PAU, repetitive imaging (CMR, CCT,

I C
or TOE) is recommended.

In complicated type B PAU, endovascular treatment (TEVAR)

I C
is recommended.

CCT, cardiovascular computed tomography; CMR, cardiovascular magnetic

resonance; PAU, penetrating atherosclerotic ulcer; TOE, transoesophageal
echocardiography; TEVAR, thoracic endovascular aortic repair

71
Traumatic aortic injury

TAI, commonly from high-speed motor accidents or falls, involves partial or

complete aorta transection. TAI is classified based on the degree of lesion
in the aortic wall.

Recommendations for traumatic aortic injury

Recommendations Class Level

In cases of severe aortic injury (grade 4), immediate repair is

I A
recommended.

In cases of TAI with suitable anatomy requiring

I A
intervention, TEVAR is recommended over open surgery.

In all TAI patients, medical therapy including pain relief, and

I C
blood pressure and heart rate control, is recommended.

In cases of TAI suspicion, CCT is recommended. I C

In cases of moderate aortic injury (grade 3), repair is

I C
recommended.

CCT, cardiovascular computed tomography; IMH, intramural haematoma;

TAI, traumatic aortic injury; TOE, transoesophageal echocardiography;
TEVAR, thoracic endovascular aortic repair.

72
Long term follow up of acute aortic syndrome

Imaging modalities and time intervals for surveillance vary according to

lesion location, type of treatment, and underlying disease (HTAD).

Recommendations for follow-up after treatment of AAS

Recommendations Class Level

After TEVAR for AAS, follow-up imaging is recommended at

1, 6, and 12 months post-operatively, then yearly until the fifth I B
post-operative year if no abnormalitiesa are documented.

In medically treated type B AAS or IMH, follow-up imaging is

recommended at 1, 3, 6, and 12 months after onset, then yearly I C
if imaging findings are stable.

In medically treated PAU, follow-up imaging is recommended

at 1 month after diagnosis, then every 6 months if imaging I C
findings are stable.

After open surgery for AAS, follow-up imaging

by CCT and TTE within 6 months, then CCT at 12 months and IIa B
then yearly if findings are stable,b should be considered.

If no complicationsa occur within the first 5 years, CCT every 2

IIa B
years thereafter should be considered.

AAS, acute aortic syndrome; CCT, cardiovascular computed tomography;

FL, false lumen; IMH, intramural haematoma; PAU, penetrating
atherosclerotic ulcer; TEVAR, thoracic endovascular aortic repair; TTE,
transthoracic echocardiography.
a
Including: pseudo-aneurysm, graft infection, endoleak (any type),
enlargement of the excluded aneurysm, and stent graft migration/
separation/fracture. bBoth in terms of extent of residual FL and of aortic
diameters at any level.

73
Genetic and congenital diseases of the aorta
Genetic and chromosomal diseases

Overview

Recommendations for the management of patients with

heritable thoracic aortic disease
Recommendations Class Level

It is recommended that medical management of patients

with HTAD is individualized and based on shared decision- I C
making.

It is recommended that patients with known or suspected

syndromic or non-syndromic HTAD are evaluated in a centre I C
with experience in the care of this patient group.

HTAD, heritable thoracic aortic disease.

74
Figure 20 Algorithm for genetic and imaging screening in patients with
thoracic aortic disease

FDR, first-degree relative; HTAD, heritable thoracic aortic disease; HTN, arterial
hypertension TAD, thoracic aortic disease; VUS, variant of uncertain significance.

75
 Recommendations for genetic testing and aortic screening in
aortic disease
Recommendations Class Level

Genetic testing

In patients with aortic root/ascending aneurysms or thoracic

aortic dissection, gathering family history information for at
I B
least three generations about TAD, unexplained sudden deaths,
and peripheral and intracranial aneurysms is recommended.

In patients with aortic root/ascending aortic aneurysms or

thoracic aortic dissection and risk factors for HTAD,a genetic
I B
counselling at an expert centre and subsequent testing, if
indicated, is recommended.

In patients with HTAD who have a pathogenic/likely pathogenic

variant, genetic testing of at-risk biological relatives (i.e. I C
cascade testing) is recommended, irrespective of age.

In patients with HTAD, guidance of clinical management by the

IIa B
underlying gene/variant, when known, should be considered.

Aortic imaging screening

In patients with TAD with risk factors for HTAD,a with a

negative family history of TAD and in whom no (likely)
I B
pathogenic variant is identified, TTEb screening aortic imaging
of FDRsc is recommended.

CCT, cardiovascular computed tomography; CMR, cardiovascular magnetic

resonance; FDR, first-degree relative; HTAD, heritable thoracic aortic
disease; TAD, thoracic aortic disease; TTE, transthoracic echocardiography.
a
See Figure 20. bCMR/CCT may be indicated if the aortic root cannot be
visualized adequately. cParents, siblings, children.

76
Turner syndrome

Turner syndrome (TS) results from partial or complete monosomy of the X-

chromosome. In newly diagnosed TS, TTE and CMR are recommended at
baseline for the evaluation of congenital heart defects and aortic anatomy/
diameters. Further follow-up is dictated by baseline aortic diameters, age,
and risk factors (Figure 21).
Figure 21 Algorithm for surveillance in women (≥15 years) with
Turner syndrome

AHI, aortic height index; ASI, aortic size index; BAV, bicuspid aortic valve;
CMR, cardiovascular magnetic resonance; CoA, coarctation of the aorta;
HTN, arterial hypertension; TTE, transthoracic echocardiography.
a
HTN: arterial hypertension, not under control with medication. bCMR if
inadequate visualization of the ascending aorta.

77
 Recommendations for imaging in women with Turner
syndrome
Recommendations Class Level

To take the smaller body size of women (≥15 years)

with TS into account, the use of the ascending ASI (ratio of
aortic diameter [mm] to BSA [m2]), AHI (ratio of aortic
I C
diameter [mm] to height [m]), or aortic z-score is recommended
to define the degree of aortic dilatation and assess the risk of
aortic dissection.

It is recommended to define imaging and clinical surveillance

intervals according to the estimated risk for dissection, based on I C
the ascending ASI and concomitant lesionsa.
AHI, aortic height index; ASI, aortic size index; BSA, body surface area; TS,
Turner syndrome.
a
Concomitant lesions: hypertension, aortic coarctation, bicuspid aortic
valve.

Vascular Ehlers Danlos syndrome

vEDS is a rare autosomal dominant disease caused by pathogenic variants

in the COL3A1 gene.
Recommendations for medical treatment in patients with vEDS
Recommendations Class Level

In patients with vEDS, regular vascular surveillance of the aorta

I C
and peripheral arteries by DUS, CCT, or CMR is recommended.

Treatment with celiprolol should be considered in patients

IIa B
with vEDS.
CCT, cardiovascular computed tomography; CMR, cardiovascular magnetic
resonance; DUS, duplex ultrasound; vEDS, vascular Ehlers–Danlos
syndrome.

78
Marfan syndrome

MFS, arises from pathogenic fibrillin-1 gene (FBN1) variants (Figure 22).
Figure 22 Algorithm for imaging surveillance in patients with
syndromic and non-syndromic heritable thoracic aortic disease

CCT, cardiovascular computed tomography; CMR, cardiovascular magnetic

resonance; TTE, transthoracic echocardiography.
a
Pre-surgical CCT. bSee respective tables of recommendations for aortic
surgery in Marfan and Loeys-Dietz syndrome in the full guidelines.

79
 Recommendations for vascular imaging in MFS
Recommendations Class Level

In patients with MFS, TTE is recommended:

At least annually in patients with an aortic root diameter <45
mm in the absence of additional risk factorsa
At least every 6 months in patients with an aortic root diameter I C
<45 mm in the presence of additional risk factorsa
At least every 6–12 months in patients with an aortic root
diameter ≥45 mm in the absence of additional risk factorsa

In patients without previous aortic surgery, complete peripheral

vascular and thoraco-abdominal aorta imaging
I C
by CMR or CCT and DUS is recommended at the first
evaluation, and subsequently every 3–5 years if stable.

In patients with MFS who have undergone aortic root

replacement, surveillance imaging of the thoracic aorta I C
by CMR (or CCT) is recommended at least every 3 years.

CCT, cardiovascular computed tomography; CMR, cardiovascular magnetic

resonance; DUS, duplex ultrasound; MFS, Marfan syndrome; TTE,
transthoracic echocardiography.
a
Risk factors: aortic root diameter >40 to ≤45 mm and family history of
aortic dissection at small aortic dimensions (i.e. <50 mm); resistant
hypertension (hypertension persisting notwithstanding three or more
antihypertensive medications prescribed by a physician with experience in
hypertension treatment); and rapid growth of the aorta (annualized growth
rate ≥3 mm or more in adults).

80
 Recommendations for medical treatment in MFS
Recommendations Class Level

In patients with MFS, treatment with either a BB or an ARB, in

maximally tolerated doses (unless contraindicated), is I A
recommended to reduce the rate of aortic dilatation.

In patients with MFS, the use of both a BB and an ARB, in

maximally tolerated doses (unless contraindicated), should be IIa A
considered to reduce the rate of aortic dilatation.

ARB, angiotensin receptor blocker; BB, beta-blocker; MFS, Marfan

syndrome.

Recommendations for aortic surgery in MFS

Recommendations Class Level

Surgery is indicated in patients with MFS who have aortic root

I B
disease with a maximal aortic sinus diameter ≥50 mm.

Surgery to replace the aortic root and ascending aorta, using the
valve-sparing surgery technique, is recommended in patients
with MFS or related HTAD with aortic root dilatation when I B
anatomical features of the valve allow its preservation and the
surgeon has specific expertise.

HTAD, heritable thoracic aortic disease; MFS, Marfan syndrome

81
In pregnant MFS women, the risk for AD increases up to eight times relative
to the general population.

Recommendations for pregnancy in women with MFS

Recommendations Class Level

It is recommended that all women with MFS:

Have a pre-conception evaluation to address the risks of
maternal CV and other complications I C
Have follow-up in a centre with access to a pregnancy heart and
vessel team.

It is recommended that couples in which a partner has or is at

I C
risk for HTAD be offered pre-conception genetic counselling.

Imaging of the whole aorta (by CMR/CCT) is recommended

I C
prior to pregnancy.

Follow-up during pregnancy is recommended with a frequency

I C
determined by aortic diameter and growth.

Intake of BBs during pregnancy is recommended. I C

Prophylactic aortic root surgery is recommended in women

I C
desiring pregnancy with aortic diameters >45 mm.

ARBs are not recommended during pregnancy. III B

BBs, beta-blockers; CCT, cardiovascular computed tomography; CMR,

cardiovascular magnetic resonance; CV, cardiovascular; HTAD, heritable
thoracic aortic disease; MFS, Marfan syndrome.

82
Recommendations for physical exercise in patients with MFS
Recommendations Class Level

It is recommended to individualize physical activity in patients

with MFS based on aortic diameter, family history of aortic I C
dissection, and pre-existing fitness.

Regular moderate aerobic exercise with a level of intensity

informed by aortic diameter is recommended in most patients I C
with MFS.

For patients who present with aortic dissection and/or have

undergone aortic surgery, post-operative cardiac rehabilitation
IIa B
aiming at improving both physical and mental health should be
considered.

MFS, Marfan syndrome.

83
Loeys Dietz syndrome

The spectrum of clinical presentations in Loeys–Dietz syndrome is very

wide. Surveillance in Loeys–Dietz syndrome is described in Figure 22.
Although the indication for surgery must be considered according to the
underlying genetic defect and the presence of risk factors (Figure 23), a 45
mm aortic diameter threshold should be considered (≥40 mm if high-risk
features).

Recommendations for imaging follow-up in Loeys–Dietz

syndrome
Recommendations Class Level

In patients with Loeys–Dietz syndrome, TTE at baseline and

subsequently every 6–12 months, depending on aortic diameter I C
and growth,a is recommended.

In patients with Loeys–Dietz syndrome, a baseline arterial

imaging study from head to pelvis with CMR or CCT and
I C
subsequent surveillance with CMR or CCT or DUS every 1–3
years is recommended.

CCT, cardiovascular computed tomography; CMR, cardiovascular magnetic

resonance; DUS, duplex ultrasound; TTE, transthoracic echocardiography.
a
More frequent imaging if aortic root/ascending diameter >42 mm and
aortic growth rate >3 mm per year.

84
Figure 23 Suggested thresholds for prophylactic aortic root/
ascending replacement in Loeys–Dietz syndrome

a,b,c,d,e,f,g,h,i Refer to full guidelines for references.

85
Recommendations for imaging and surgery in ACTA2-related
heritable thoracic aortic disease
Recommendations Class Level

Annual monitoring of the aortic root/ascending aorta

with TTE to evaluate aortic root/ascending aorta enlargement is I C
recommended.

Imaging of the aorta with CMR/CCT every 3–5 years is

I C
recommended.

CCT, cardiovascular computed tomography; CMR, cardiovascular magnetic

resonance; TTE, thoracic echocardiography.

86
Aortic disease associated with bicuspid aortic valves
When a BAV is first detected, a complete study of the thoracic aorta is necessary; vice
versa, in every patient with ascending aortic dilatation, valve morphology should be
ascertained.

Recommendations for BAV-associated aortopathy

management
Recommendations Class Level

When a BAV is first diagnosed, initial TTE to assess diameters of

I B
the aorta at several levels is recommended.

Surgery for bicuspid aortopathy is recommended when the

I B
maximum aortic diameter is ≥55 mm.

Surgery for bicuspid aortopathy of the root phenotypea is

I B
recommended when the maximum aortic diameter is ≥50 mm.

CCT or CMR of the entire thoracic aorta is recommended at first

diagnosis and when important discrepancies in measurements are
I C
found between subsequent TTE controls during surveillance, or
when the diameter of the aorta exceeds 45 mm.

Screening by TTE in FDRs of BAV patients with root

phenotypea aortopathy and/or isolated aortic regurgitation is I C
recommended.

Surveillance serial imaging by TTE is recommended

in BAV patients with a maximum aortic diameter >40 mm, either
I C
with no indication for surgery or after isolated aortic valve surgery,
after 1 year, then if stability is observed, every 2–3 years.

Screening by TTE in FDRs of all BAV patients should be

IIa B
considered.

In patients with low surgical risk, surgery for bicuspid aortopathy of

ascending phenotypeb should be considered when the maximum IIa B
aortic diameter is >52 mm.

87
BAV, bicuspid aortic valve; BP, blood pressure; CCT, cardiovascular
computed tomography; CMR, cardiovascular magnetic resonance; CSA/h,
cross-sectional area-to-height ratio; FDRs, first-degree relatives; TTE,
transthoracic echocardiography.
a
Root phenotype = aortic dilatation with sinus diameter > tubular
diameter. bAscending phenotype = aortic dilatation with tubular diameter >
sinus diameter.

Polyvascular PAD and PAD in patients with cardiac

diseases

Polyvascular disease (PVD) is defined as the simultaneous presence of

clinically relevant obstructive atherosclerotic lesions in at least two major
arterial territories.

88
 Recommendations for screening and management of
polyvascular disease and PAD with cardiac diseases
Recommendations Class Level

In patients with PVD, an LDL-C reduction by ≥50% from

baseline and an LDL-C goal of <1.4 mmol/L (<55 mg/dL) are I A
recommended.

In patients with PAD and newly diagnosed AF with

a CHA2DS2-VASc score ≥2, full oral anticoagulation is I C
recommended.

Screening for ilio-femoral PAD is recommended in patients

I B
undergoing TAVI.

Carotid DUS should be considered for stable patients scheduled

for CABG with TIA/stroke within the past 6 months without IIa B
carotid revascularization.

In patients with stable PVD who are symptomatic in at least one

territory and without high bleeding risk,a treatment with a
IIa A
combination of rivaroxaban (2.5 mg b.i.d.) and aspirin (100
mg o.d.) should be considered.
AF, atrial fibrillation; b.i.d., twice daily; CABG, coronary artery bypass
grafting; CHA2DS2-VASc, congestive heart failure, hypertension, age ≥75
(doubled), diabetes, stroke (doubled), vascular disease, age 65 to 74 and
sex category (female); DUS, duplex ultrasound; eGFR, estimated glomerular
filtration rate; LDL-C, low-density lipoprotein cholesterol; o.d., once daily;
PAD, peripheral arterial disease; PVD, polyvascular disease; TAVI,
transcatheter aortic valve implantation; TIA, transient ischaemic attack.
a
Prior history of intracerebral haemorrhage or ischaemic stroke, history of
other intracranial pathology, recent gastrointestinal bleeding or anaemia
due to possible gastrointestinal blood loss, other gastrointestinal pathology
associated with increased bleeding risk, liver failure, bleeding diathesis or
coagulopathy, extreme o.d age or frailty, or renal failure requiring dialysis or
with eGFR <15 mL/min/1.73 m2.

89