Hypertension

REVIEW

Digital Therapeutics in Hypertension: Evidence

and Perspectives
Kazuomi Kario , Noriko Harada, Ayako Okura

ABSTRACT: Digital therapeutics refers to the use of evidence-based therapeutic interventions driven by high-quality software
programs to treat, manage, or prevent a medical condition. This approach is being increasingly investigated for the management
of hypertension, a common condition that is the leading preventable cardiovascular disease risk factor worldwide. Digital
interventions can help facilitate uptake of important guideline-recommended lifestyle modifications, reinforce home blood
pressure monitoring, decrease therapeutic inertia, and improve medication adherence. However, current studies are only
of moderate quality, and are highly heterogeneous in the interventions evaluated, comparator used, and results obtained.
Therefore, additional studies are needed, focusing on the development of universally applicable and consistent digital
therapeutic strategies designed with health care professional input and evaluation of these interventions in robust clinical
trials with objective end points. Hopefully, the momentum for digital therapeutics triggered by the coronavirus disease 2019
pandemic can be utilized to maximize advancements in this field and drive widespread implementation.

Key Words: blood pressure ◼ cardiovascular diseases ◼ digital technology ◼ hypertension ◼ mobile applications

D
igital health essentially refers to the use of digital in the areas of smoking cessation,4 mental health,5 dia-
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technologies for health.1 It involves the use of infor- betes,6,7 and hypertension.8 Recently, monitoring of blood
mation and communications technology (ICT; ie, pressure (BP) at home and associated digital solutions
digital technologies) to support health and health-related received a big push due to the requirement for remote
fields.1 Digital health is facilitated by access to real-time patient management during lockdowns implemented in
information via constantly evolving digital technologies. response to the COVID-19 pandemic.9–13
In addition to improving the quality of patient care, this Hypertension has a high global prevalence and is the
approach can also help to increase the productivity, effi- leading preventable cardiovascular disease risk factor
ciency, and accessibility of health care provision.2 Digi- worldwide.14,15 However, despite the availability of a range
tal health is a broad term that covers digital medicine of pharmacological treatment options, BP control is often
(the subset of digital health that relates to the use of suboptimal.15 This means that there is a potential role
technology to facilitate medical care and treatment) and for digital therapeutic interventions as a complementary
then, more specifically, both software as a medical device strategy to optimize the management of hypertension.
(software used for medical purposes that are not part Despite the widespread availability of apps claiming
of a hardware medical device) and digital therapeutics to facilitate hypertension control or medication adher-
(Figure 1). Digital therapeutics “deliver to patients evi- ence,16 not many have been developed in collaboration
dence-based therapeutic interventions that are driven by with health care professionals, been validated, or under-
high-quality software programs to treat, manage, or pre- gone rigorous scientific assessment of BP-lowering effi-
vent a medical disorder or disease. They are used inde- cacy.17,18 Furthermore, despite current applications, there
pendently or in concert with medications, devices, or other is a relative lack of data relating to digital therapeutics
therapies to optimize patient care and health outcomes.”3 in hypertension management. However, it is essential
Digital medicine and digital therapeutics approaches to that digital solutions for hypertension management are
patient management have already been widely utilized evidence-based and effective to minimize the impact of

Correspondence to: Kazuomi Kario, Division of Cardiovascular Medicine, Department of Medicine, Jichi Medical University School of Medicine, 3311-1 Yakushiji,
Shimotsuke, Tochigi 329-0498, Japan. Email [email protected]
For Sources of Funding and Disclosures, see page 2156.
© 2022 American Heart Association, Inc.
Hypertension is available at www.ahajournals.org/journal/hyp

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 Kario et al Digital Therapeutics in Hypertension

interaction, and patient-doctor interaction, all of which

Nonstandard Abbreviations and Acronyms combine to facilitate a shared goal of lifestyle improve-
ment and target BP attainment (Figure 2). There are sev-
App application eral key steps including obtaining individual patient data

Review
BP blood pressure and providing interactive education, providing personal-
HBPM home BP monitoring ized intervention based on these data, and self-planning
ICT information and communications and evaluation (supported by the personalized interven-
technology tion). The course of the intervention may not always be
mHealth mobile health linear, with a role for things like education multiple times
SBP systolic BP during the process. Together, these features help to
STEP Strategy of Blood Pressure Intervention
establish a personalized approach based on real-world
in the Elderly Hypertensive Patients data and evidence (Figure 3).
The wide variety of potential data inputs into an ICT
platform for digital therapeutics in hypertension means
this important contributor to the worldwide epidemic of that there is currently a large array of mobile applications
noncommunicable diseases. This narrative review article and software technologies that have been designed to
provides an overview of digital therapeutics in hyperten- aid in the management of the disease. This means that
sion, including the design and features of different digital there is a general lack of consistency in approach, and no
therapeutics platforms, current randomized controlled one method currently predominates.
studies for mobile application (app) use, limitations, and
potential apps. Key publications in the field were identi-
fied by PubMed searches conducted in October 2021 POTENTIAL BP-LOWERING MECHANISMS
using the search terms “Digital therapeutics” or “mobile OF DIGITAL THERAPEUTICS IN
app” or “digital health” and “hypertension”. Search hits HYPERTENSION
were restricted to English language publications. Refer-
Effective digital therapeutics for hypertension include
ence lists of articles identified in the search were also
specific mechanisms to decrease BP, independent of
reviewed to identify additional relevant publications.
pharmacotherapy and adherence. One of the broad mech-
However, it should be noted that this process may result
anisms underlying the benefits of digital therapeutics is
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in some biases, including publication bias and the exclu-

biofeedback to improve monitoring and management.
sion of non-English language materials.
More specifically, there are many potential mechanisms
that contribute to the BP-lowering effects of digital thera-
peutic interventions in patients with hypertension. First,
ICT PLATFORM FOR DIGITAL
there is the impact of these interventions on the imple-
THERAPEUTICS mentation of, and adherence to, guideline-driven/evi-
In digital therapeutics, ICT is used to store, retrieve, dence-based important nonpharmacological interventions
share, and exchange health-related information to sup- for reducing BP. These include consumption of a healthy
port the prevention, diagnosis, treatment, and monitor- diet (reduced intake of saturated fatty acids and cho-
ing of hypertension.19 This is facilitated by the now lesterol; increased intake of polyunsaturated fatty acids
widespread availability of smartphones and tablets. In and low-fat dairy products), reducing dietary salt intake,
addition, a shared internet-based platform enables col- increasing dietary consumption of potassium, increasing
laborative care and interactions between stakeholders.19 physical activity, reducing body weight, moderating alcohol
This connected infrastructure of health systems and intake, stress management, and good sleep hygiene (Fig-
services is also referred to as the “Internet of Medical ure 3).21–28 There are good levels of evidence to support
Things.”20 Contributors to the Internet of Medical Things all these approaches to BP reduction.21–28 Of the lifestyle
include the patient, health care professionals involved modifications recommended by the guidelines, decreasing
in their care, and devices that collect medical informa- salt intake is particularly important in reducing BP, espe-
tion (eg, smartphone, tablet, connected BP monitor), and cially in Asian patients with hypertension.21 Decreasing
potentially other environmental signals (eg, temperature, salt intake by use of a salt substitute was recently shown
humidity, air pollution). With data storage in the cloud, all to reduce rates of cardiovascular disease events, stroke,
this information is then available to stakeholders involved and all-cause mortality in rural Chinese adults aged ≥60
in patient care, including the hospital/clinic/health care years with hypertension and a history of cardiovascular
provider, the patient, and relevant health care profession- disease.29 The different components may also interact.
als (eg, physician, nurse, pharmacist). For example, both stress reduction and decreased alco-
Elements of a digital therapeutics platform for hyper- hol intake could contribute to better sleep quality.30,31 In
tension include patient-app interaction, app-doctor addition, exercise might make a greater contribution to

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 Kario et al Digital Therapeutics in Hypertension
Review
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Figure 1. Key definitions and keywords.

DTx indicates digital therapeutics; and ICT, information and communications technology.

weight loss, which in turn reduces BP,32,33 rather than hav- limits access to those who have the ability to pay for one.
ing a direct BP-lowering effect. However, there is not yet Access issues such as this are a key factor that needs to
enough data to draw any firm conclusions. be overcome if digital therapeutics are to be implemented
Self-monitoring of BP using a home BP monitoring in a widespread and equitable manner.
(HBPM) device is another essential component of digi- Meta-analysis data show that self-monitoring of BP
tal therapeutics in patients with hypertension (Figure 3). by itself can reduce both systolic and diastolic BP, and
Use of out-of-office BP monitoring, including HBPM, is increase the proportion of patients with normalization of
preferred over office BP monitoring for the diagnosis and BP.39 Furthermore, data from randomized clinical trials
management of hypertension in major hypertension guide- indicate that app-related interventions for enhanced BP
lines.21–23 This is because home BP has been shown to be self-monitoring and feedback are beneficial for improving
a better predictor of cardiovascular outcomes than office BP control, especially when BP control is inadequate.40
BP.34,35 Transmission of objective HBPM data is essential The addition of other interventions such as education,
for the evaluation of changes in BP over time (eg, after management of drug therapy, adherence monitoring,
the initiation of lifestyle modifications or drug therapy), and counseling, and behavioral interventions—all of which
provides important information on BP variability (beat-to- could be incorporated into a digital therapeutics interven-
beat, day-to-day, seasonal, etc), which is another important tion—decreased BP to a greater extent than BP monitor-
cardiovascular risk factor.36 However, home BP record- ing alone.41 On the basis of these meta-analysis findings,
ings are only useful if they are accurate. Therefore, use it was concluded that implementation of self-monitoring
of a validated HBPM device is essential to allow high- of BP should be accompanied by other interventions to
quality measurements of home BP.21–23,37 Increasing use facilitate sufficient and optimal BP lowering.41 This sug-
of digital therapeutics could help to facilitate access to gests that high-quality digital therapeutic interventions
appropriately validated HBPM devices, something that is that address a wide range of measures are needed to
currently an important issue.38 Despite their value, HBPM effectively reduce BP and lower cardiovascular risk in
devices are not currently reimbursed in any country, which patients with hypertension.

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 Kario et al Digital Therapeutics in Hypertension

Review
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Figure 2. Components of a theoretical digital therapeutics platform for hypertension: interactive approach for optimized
personalized intervention.
BP, blood pressure.

Finally, improvements in medication adherence and with hypertension is growing, with the majority of studies
optimization of antihypertensive drug therapy are addi- published in the last 3 years (Table). Currently available
tional potential mechanisms by which digital therapeu- studies are of moderate quality only, with the main issue
tic interventions could contribute to reductions in BP in that could introduce bias being lack of blinding. Although
patients with hypertension. Both medication nonadher- this might be difficult to achieve in digital intervention
ence and prescribing inertia are important contributors trials, it is something that will need to be addressed to
to suboptimal control of BP in patients with hyperten- ensure that trials in this field provide high-quality, unbi-
sion.42,43 Therapeutic inertia in hypertension refers to the ased data that can be used to inform clinical practice.
failure of providers to initiate new therapy or titrate exist- Another important thing to note about currently avail-
ing therapy when BP targets are not achieved.44 Improv- able data on mHealth app intervention in hypertension is
ing medication adherence or reducing therapeutic inertia the lack of consistency. This includes lack of consistency
(or ideally both of these factors) would be expected to in the interventions evaluated, the definition of the stan-
improve the utilization and effectiveness of pharmaco- dard care comparator, and in study findings. The resulting
logical antihypertensive therapy. In fact, better compli- heterogeneity, along with the potential for bias, makes
ance with antihypertensive medication has been shown it difficult to draw conclusions regarding the usefulness
to reduce cardiovascular risk.45 of interventions overall and to determine which aspects
of digital health strategies might be most important for
facilitating reductions in BP. In addition, there are not yet
CURRENT RANDOMIZED CONTROLLED any truly large-scale clinical trials of mHealth app inter-
ventions in patients with hypertension.
STUDIES Three randomized studies have included a sample
The body of evidence for the BP-lowering effects of size of >300 patients (Table).46–48 Of these 2 showed
mobile health (mHealth) app interventions in patients a significant reduction in BP in the digital therapeutics

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 Kario et al Digital Therapeutics in Hypertension
Review

Figure 3. Digital therapeutics process for hypertension (lifestyle modifications based on personalized analysis).
BP indicates blood pressure.

group,46,47 whereas one did not.48 The largest positive The other large, positive study utilized a more compre-
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study was conducted in untreated patients with essential hensive app, which included reminders to measure BP, take
hypertension (n=390) and used a digital therapeutics medicine and exercise, alerts when physician visits were
intervention specifically designed to promote lifestyle due, records of BP, BP control and drug use, education
modifications (the HERB system; CureApp, Inc).47 App modules, and health evaluations, and allowed users to have
users created a personalized profile that included data remote physician consultations.46 A total of 480 patients
on age, sex, lifestyle, social background, and behav- were enrolled and followed for 6 months; the primary end
ior patterns. This information was combined with home point was the change from baseline in SBP and diastolic
BP measurements to develop a personalized program BP in the intervention group compared with control (no
of lifestyle modifications designed to reduce BP.47 This use of digital interventions). Both SBP and diastolic BP
included an interactive education program (step 1), spe- decreased from baseline to a significantly greater extent in
cific instructions to implement lifestyle modifications the digital therapeutics versus control group, and the pro-
(step 2), and self-planning and evaluation (step 3). Mean portion of patients with BP control at the end of the study
changes in ambulatory systolic BP (SBP) from baseline was also significantly higher in the intervention group.46
to 12 weeks (the primary end point) were significantly The large study that did not show any significant ben-
greater in the intervention versus control group (man- efit from digital therapeutics usage included patients with
aged using standard lifestyle modifications), as were uncontrolled or poorly controlled hypertension.48 It used a
home and office SBP. The mobile app engagement rate smartphone coaching app designed to promote behavioral
was high (98.1%) and no program-related safety events changes associated with hypertension self-management.48
occurred.47 A smaller study has also shown the utility of a There were no significant differences in the change from
mobile app for helping patients adhere to lifestyle modi- baseline in SBP compared with the control group in either
fications and improve medication adherence.49 In addi- study, although the self-management app did significantly
tion, another small study of a mobile app–based disease improve patient confidence in BP control.48 Another inter-
management program showed that positive changes in vention that has been shown to significantly reduce BP
measures of patient activation were significantly asso- compared with standard care in a smaller study is a tablet-
ciated with improvement in lifestyle measures including based disease self-monitoring system.51
alcohol consumption and cigarette smoking, as well as Overall, there is a growing body of data on the use of
SBP and diastolic BP.50 mHealth app interventions in hypertension management,

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 Kario et al Digital Therapeutics in Hypertension

Table. Summary of Studies Reporting the Effects of mHealth App Interventions Relating to Lifestyle Interventions on Blood
Pressure in Patients With Hypertension

Design Primary outcome

(duration of (key secondary Digital interven- Quality of

Review
Author, year Patients (n) follow-up) outcome) tion/ control Findings evidence*
Kario et al, HTN (n=146) Multicenter, Mean change in Mobile app–based Mean change from baseline in 24-h ambulatory 3
202160 randomized, 24-h SBP by ABPM support for lifestyle BP did not differ significantly between the DTx
open, pilot at 24 wk (mean modifications and std care groups (adjusted difference, −0.66
study (24 wk) change in 24-h SBP (HERB)/Std care (95% CI, −5.34 to 3.9; P=0.78)
by ABPM at 16 wk)
Kario et al, Untreated HTN Multicenter, Mean change in 24-h Mobile app–based Between-group differences (95% CI) in the 3
202147 (n=390) randomized, SBP by ABPM at 12 support for lifestyle change from baseline in 24-h ambulatory, home,
open (12 wk) wk (Mean changes modifications and office SBPs were −2.4 (−4.5 to −0.3)
in office and home (HERB)/Std care [P=0.034], −4.3 (−6.7 to −1.9) [P<0.001], and
BP at 12 wk) −3.6 (−6.2 to −1.0) mm Hg [P=0.006], respec-
tively. The proportion of patients achieving morn-
ing home BP <135/85 mmHg was 22.2% in the
DTx group and 10.4% in the control group. The
mobile app engagement rate was 98.1%
Bozorgi et al, HTN (n=120) Randomized, Adherence to antihy- Mobile app–based MAP decreased over time by 3.4 mm Hg (95% 3
202149 open (24 wk) pertensive medica- education support/ CI, 1.6 to 5.2), and adherence to treatment was
tion (Regular BP Std care better, in the mHealth app vs std care group
monitoring)
Gong et al, HTN (n=480) Multicenter, SBP and DBP Mobile app–based Mean change from baseline in SBP was 3
202046 randomized, changes at 6 mo HTN management/ −8.99±6.42 in the mHealth app group and
open (6 mo) (Medication adher- Std care −5.92±9.5 mm Hg in the std care group (P<0.05
ence) for between-group difference in change from
baseline). The proportion of pts with BP control at
the end of the study was 77% in the mHealth app
group vs 67% in the std care group (p<0.001)
Persell et al, Uncontrolled Randomized, SBP at 6 mo with Mobile coaching Adjusted between-group difference in mean 3
202048 HTN (n=333) open (6 mo) prespecified adjust- app/BP-tracking SBP at 6 mo was −2.0 mm Hg (95% CI −4.9 to
ment for baseline app (control) 0.8); P=0.16; self-confidence in controlling BP
SBP, sex, and age score was greater in the mobile Coaching app
(self-reported antihy- vs control group (P<0.001)
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pertensive medica-
tion adherence)
Kim et al, HTN (n=95) Randomized Not predefined Mobile app–based In multivariable models, the interaction between 2
201650 (sub-study), disease manage- wireless self-monitoring and positive changes in
open (6 mo) ment program/Std the patient activation measure was a significant
care contributor to improvements in cigarette smok-
ing, alcohol consumption, SBP, and DBP
Or et al, T2D±HTN Randomized, HbA1c level, fasting Tablet-based inter- The decrease from baseline in mean SBP (95% 3
201651 (n=63) open, pilot blood glucose level, active self-monitor- CI) was −13.0 mm Hg (−19.1 to −6.9) in the
study (3 mo) SBP, DBP, chronic ing system including mHealth app group vs −5.4 mm Hg (−12.0 to 1.1)
disease knowledge, reminders and in the std care group (P=0.043). There were no
and frequency of education materials/ significant between-group differences in frequency
self-monitoring at 1, Self-monitoring only of BP and fasting blood glucose monitoring,
2, and 3 mo. (std care) chronic disease knowledge, or levels of fasting
blood glucose or glycosylated hemoglobin

ABPM indicates ambulatory BP monitoring; app, application; BP, blood pressure; DBP, diastolic BP; DTx, digital therapeutics; HbA1c, glycated hemoglobin; HTN,
hypertension; MAP, mean arterial pressure; mHealth, mobile health; pts, patients; SBP, systolic blood pressure; std, standard; and T2D, type 2 diabetes.
*Jadad score, on a scale from 0 to 5 where higher scores indicate higher quality and less risk of bias.

although the quality of evidence is moderate. Aggre- interventions in robust clinical trials with objective end
gating available data, a recent meta-analysis reported points. The ultimate goal would be to investigate and doc-
decreases in BP and increases in medication adherence ument a beneficial effect of digital interventions that are
in patients with hypertension who used smartphone acceptable to both patients and health care profession-
apps.52 However, the heterogeneous nature of current als not only on BP but also on cardiovascular outcomes.
studies with respect to both interventions and results
means that additional research is needed. This should
focus on the development of more universally applicable COMPREHENSIVE DIGITAL APPROACH
and consistent digital therapeutic strategies with input
from both health care professionals and patients (the lat- FOR BP VARIABILITY
ter do not appear to have been involved in the design of Although hypertension is a well-documented cardio-
currently available digital tools) and evaluation of these vascular risk factor, there are multiple mechanisms

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 Kario et al Digital Therapeutics in Hypertension

underlying this increased risk. Elevated BP itself is a risk might be evaluation of day-by-day interactions between
factor for progressive endothelial dysfunction and ath- the patient’s behavior and the BP response during use of
erosclerosis.53,54 Then, in the presence of existing cardio- a digital tool. This might be facilitated by the use of wear-
vascular disease, exaggerated BP variability can trigger able sensors, including cuff-less BP monitoring.61
Review

acute cardiovascular events.55 These relationships have

been described using the resonance hypothesis.56
In the context of cardiovascular disease, anticipation USE WITH OTHER ANTIHYPERTENSIVE
medicine is defined as practices that help to predict the THERAPIES
time and place of cardiovascular event onset by record-
Digital therapeutics have a role across the continuum
ing relevant parameters and providing alerts when risk is
of hypertension management, from the early stage right
increasing, thus allowing proactive, real-time risk reduc-
through to end-stage cardiovascular or renal disease.
tion.57,58 Therefore, a digital therapeutics system that
As a result, they are almost certain to be combined with
utilizes ICT to monitor both BP measurements and BP
other pharmacological or nonpharmacological treatments
variability taking into account other stressors, including
for hypertension. Renin-angiotensin system inhibitors or
environmental factors, would be ideally suited to facilitate
diuretics might have synergistic effects in combination
anticipation medicine.
with digital therapeutic strategies with respect to salt
Such a system has been developed, known as
reduction, but this needs to be evaluated further. In early-
ICT-based multisensory ambulatory BP monitoring
stage hypertension, there is the potential for utilization of
(IMS-ABPM; A&D Co, Tokyo, Japan). It includes a high-
digital therapeutics promoting lifestyle modifications to
sensitivity actigraph that detects the wearer’s fine-scale
delay or eliminate the need for drug therapy, or to allow
physical movements in three directions, a thermometer
this to be initiated at a lower dosage. Then, when needed,
and a barometer.59 The system stores BP and waveform
digital monitoring can facilitate adherence to, and optimi-
data from intracuff pressure, which is transmitted to a
zation of, drug therapy as has been already reported.49,62
data center for analysis, and the results are shared with
Digital therapeutic strategies might also help physicians
both the patient and their doctor. Artificial intelligence
to identify good candidates for renal denervation, and
could be applied to the cloud-based big data (Internet of
could be continued to support BP reductions after this
Medical Things) to assess time-series of BP changes to
procedure (Figure 4). Additionally, digital therapeutics
predict future BP variability. For a comprehensive digital
modules that specifically target other cardiometabolic
approach, this system could be combined with an app
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risk factors, such as obesity, diabetes, and hyperlipid-

that stores personalized data on knowledge, attitude,
emia, could be added to those targeting hypertension to
and practice relating to hypertension and cardiovascular
further reduce risk.
disease, and required lifestyle modifications (such as, for
example, the recently developed HERB system60). Taken
together, the data obtained and generated by this digi-
tal solution would provide real-time feedback to patients
and physicians and potentially contribute to the preven-
tion of adverse BP-related and BP variability–related
cardiovascular outcomes. This is an important area for
future research.

IDENTIFYING RESPONDERS
Based on the limited amount of current data, patients
with hypertension who are motivated to change their
health behavior might be the best candidates for mobile
app–based self-monitoring of health.50 Otherwise, it is
not yet clear which patients will respond best to mHealth
app interventions. This is made even more challenging by
the lack of consistency in the digital strategies studied
to date and the heterogeneous results of those stud-
ies. Grouping patients, or patient phenotyping, based on
factors or characteristics known to be associated with Figure 4. Potential mechanisms contributing to the blood
hypertension, including salt or alcohol intake, stress, pressure (BP)–lowering effects of digital therapeutic
interventions for hypertension, including lifestyle
sleep quality, and environmental factors (eg, tempera- modifications (blue boxes), BP monitoring (purple box), and
ture, air pollution) may be helpful. Another approach to optimization of pharmacological therapy (black boxes).
identifying those likely to respond to digital intervention DTx indicates digital therapeutics.

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 Kario et al Digital Therapeutics in Hypertension

promising digital interventions into data platforms of

health care providers.
In a similar vein, the impact of cultural and regional
factors on the acceptability or effectiveness of digital

Review
health interventions is not yet known. Therefore, whether
or not there are characteristics or influences that might
render some digital strategies less useable or ineffective
in certain settings needs to be investigated further.
Individuals with lower levels of technology literacy (eg,
older patients) might not have access to, or be able to use,
a smartphone and digital therapeutic apps. However, it
was encouraging that 95.8% of elderly patients in STEP
study (the Strategy of Blood Pressure Intervention in the
Elderly Hypertensive Patients) used the smartphone app
Figure 5. Digital therapeutics as one component of patient- to transmit home BP readings.64 Low ICT skill level, lack of
centered hypertension management. motivation, lack of awareness of the usefulness of strate-
gies, such as telemedicine, or resistance to adopting new
treatment paradigms, could also be barriers to the uptake
LIMITATIONS of these methodologies for physicians as well as patients.65
Despite the promise of digital therapeutic interventions, Furthermore, health care professionals will need to be edu-
there are several limitations that can impact on the dis- cated about the application and implementation of digital
semination and adoption of these approaches in routine therapeutics, which could differ substantially from the tra-
clinical practice. Access to technology such as a smart- ditional model of face-to-face care.65
phone and the internet, from both cost and logistical per- Digital therapeutics relies on technology and equip-
spectives, may be an issue that precludes the widespread ment that should be developed, validated, and certified
implementation of ICT-based digital therapeutics in some based on regulatory requirements.65 Regulatory bodies
regions or in specific vulnerable populations. There is also in the United States and Europe have outlined the con-
the issue of reimbursement, which would be required ditions under which medical software is classified as a
to facilitate more widespread accessibility and uptake. medical device and, as a result, the regulation and valida-
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Issues relating to reimbursement of health care profes- tion process.66,67 However, there are currently no specific
sionals for services and consultations as part of digital regulatory standards for digital therapeutics, either within
interventions also need to be evaluated and addressed. or across countries. These standards and quality control
Another important systems-related limitation is that guidelines will be important to ensure that things like the
none of the digital therapeutics approaches studied to educational components of digital therapeutic interven-
date have been fully integrated into existing health care tions are scientifically accurate and evidence-based. In
systems. Therefore, the impact of these interventions in addition, systems that incorporate self-measurement of
the context of overall health management and their abil- BP are only going to be as good as the BP data recorded,
ity to be integrated into existing infrastructure (eg, elec- which reinforces the need for the use of validated mea-
tronic medical records) is not yet known. As noted by the surement tools as part of digital therapeutics in hyper-
World Health Organization, increasing interest in digital tension. Further research and development are needed
health has meant that these interventions have been to support the development of validated, guideline-driven
implemented without a careful examination of available digital therapeutic strategies in hypertension. One tool that
evidence relating to benefits and harms (which is often might be useful to inform this process is artificial intel-
limited).1 The drive to incorporate digital health solutions ligence, potentially in combination with data from wear-
(fueled by the COVID-19 pandemic) has resulted in rise able monitoring devices.61 However, it is important to note
in the use of an overwhelming diversity of digital tools, that there are several hurdles to overcome before artificial
many of which are short-lived, without fully understanding intelligence can be reliably implemented to transform the
their impact on health care systems and the well-being management of hypertension.68 In addition, there is the
of individuals.1 The concerns driven by these issues were potential for unintended consequences with exclusive use
summarized in the consensus statement of the WHO Bel- of predictive artificial intelligence-based models if correla-
lagio eHealth Evaluation Group, which opened by stating: tions are mistaken for causation.68 Other relevant issues
“to improve health and reduce health inequalities, rigorous in the application of artificial intelligence are the quality of
evaluation of eHealth is necessary to generate evidence data used to inform machine learning and models, and the
and promote the appropriate integration and use of tech- potential for machine learning to reflect existing societal
nologies.”63 Thus, additional work is needed to undertake biases to the disadvantage of those already experiencing
the substantial extra steps required to translate new and health disparities (eg, ethnic minorities).68

Hypertension. 2022;79:2148–2158. DOI: 10.1161/HYPERTENSIONAHA.122.19414 October 2022   2155

 Kario et al Digital Therapeutics in Hypertension

An individual’s health-related information is highly sen- Acknowledgments

sitive, and this is especially relevant when data are being Medical writing assistance was provided by Nicola Ryan, independent medical
writer, funded by Jichi Medical University. K. Kario and N. Harada conceptualized
collected and stored on digital platforms. Concerns about this review and researched for contents. A. Okura assisted in the literature search.
these issues may prevent some patients from participating
Review

All authors contributed to the writing of the final article.

in digital therapeutic solutions. Therefore, safeguards are
Sources of Funding
needed to ensure the privacy and safety of patient data None.
and to minimize the risk of any data leaks or breaches.
These reassurances then need to be passed on to patients. Disclosures
K. Kario reports grants from CureApp Inc. outside the submitted work. The other
Applicable laws and regulations in Europe69 and the Health
authors report no conflicts.
Insurance Portability and Accountability Act in the United
States70 currently do provide a level of protection and can
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