Zhao et al.

Cardiovascular Diabetology (2025) 24:185 Cardiovascular Diabetology

https://doi.org/10.1186/s12933-025-02678-9

RESEARCH Open Access

Cardiorenal protection with dapagliflozin

in patients with type 2 diabetes mellitus
and chronic coronary syndrome undergoing
percutaneous coronary intervention:
a registry cross-sectional study
Zinan Zhao1, Naixin Zheng2, Tianqi Zhang1, Chi Zhang3, Yuwei Li2, Ming Lan2, Ni Zhang2, Hui Li2, Hu Ai2 and
Deping Liu2*

Abstract
Importance Although sodium‒glucose cotransporter-2 (SGLT2) inhibitors have cardiorenal benefits, their efficacy
in patients with type 2 diabetes mellitus (T2DM) and chronic coronary syndrome (CCS) undergoing percutaneous
coronary intervention (PCI) remains underexplored.
Objective To evaluate the cardiorenal protective effects of the SGLT2 inhibitor dapagliflozin in patients with T2DM
and CCS receiving PCI.
Design, setting, and participants This was a cross-sectional analysis of 1,430 patients from a tertiary hospital
database who underwent PCI (January 1, 2018, to March 31, 2022).
Main outcomes and measures Cardiac outcomes (PMI/4aMI) and renal outcomes (eGFR and CI-AKI).
Results After 1:1 propensity score matching (PSM) (176 dapagliflozin vs. 176 control), the dapagliflozin group
showed significantly lower PMI/4aMI rates pre-PSM (39.78% vs. 66.99%; OR 0.862, 95% CI 0.823–0.904; p < 0.001) and
post-PSM (39.77% vs. 60.23%; OR 0.660, 95% CI 0.531–0.821; p < 0.001), with sustained significance after adjustment
(adjusted OR 0.436, 95% CI 0.285–0.668; p < 0.001). Subgroup analyses highlighted increased protection in patients
aged ≥ 65 years, those with multivessel disease, and those with higher contrast volumes. Renal outcomes (CI-AKIESUR
and CI-AKIKDIGOs) were not significantly different before or after PSM or after adjustment (all p > 0.05).
Conclusions and relevance Dapagliflozin exerted robust cardioprotective effects against PMI/4aMI in patients with
T2DM and CCS undergoing PCI, particularly among patients in high-risk subgroups, but it did not significantly reduce
the risk of CI-AKI. These findings support the peri-PCI use of dapagliflozin to mitigate cardiac risk while highlighting
the need for further research to elucidate its renal effects in this population.

*Correspondence:
Deping Liu
[email protected]
Full list of author information is available at the end of the article

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Zhao et al. Cardiovascular Diabetology (2025) 24:185 Page 2 of 12

Keywords Dapagliflozin, SGLT2 inhibitors, Cardiorenal protection, Type 2 diabetes mellitus, Chronic coronary
syndrome, Percutaneous coronary intervention
Graphical abstract

Research insights Supports peri-PCI dapagliflozin use for cardiac risk

What is currently known about this topic? reduction in high-risk T2DM-CCS patients.

1. SGLT2 inhibitors reduce cardiorenal risks in T2DM Introduction

and CVD patients. Sodium‒glucose cotransporter 2 (SGLT2) inhibitors
2. Controversy exists on SGLT2 inhibitors’ renal lower blood glucose levels by inhibiting glucose reab-
benefits post-PCI. sorption in the renal proximal tubule, and they were first
indicated for the treatment of type 2 diabetes mellitus
What is the key research question? (T2DM) [1]. SGLT2 inhibitors have shown cardiorenal
protective properties and are particularly beneficial in
Does dapagliflozin provide cardiorenal protection in patients with cardiovascular disease (CVD) and chronic
T2DM and CCS patients undergoing PCI? kidney disease (CKD) complicated by T2DM [2].
Several theories propose that the cardiovascular effects
What is new? of SGLT2 inhibitors are mediated by the inhibition of
sodium-hydrogen exchanger 1 (NHE1) in heart muscles
1. First study linking dapagliflozin to reduced PMI/4aMI and sodium-hydrogen exchanger 3 (NHE3) in the proxi-
in T2DM-CCS-PCI patients. mal tubules of the kidneys. NHE3 is responsible for most
2. Dapagliflozin showed cardiac protection but no electrolyte and water reabsorption in the kidneys, thus
significant CI-AKI reduction. reducing the preload via diuresis and natriuresis [3]. In
3. Enhanced benefits in elderly, multivessel disease, and the proximal convoluted tubules (PCTs) of the kidney,
high-contrast subgroups. SGLT2s are observed where maximal glucose reab-
sorption occurs in the blood. SGLT2 inhibitors block
How might this study influence clinical practice? these transporters in the PCTs of the kidneys, causing
Zhao et al. Cardiovascular Diabetology (2025) 24:185 Page 3 of 12

glucosuria, which helps lower blood glucose levels in myocardial infarction (PMI) or type 4aMI. The defini-
patients with T2DM [4]. tion of PMI was a > 5 × 99th percentile upper reference
In patients with T2DM and heart failure (HF), SGLT2 limit (URL) increase in cardiac troponin I (cTnI) within
inhibitors, including dapagliflozin, have shown protec- 48 h of the procedure. The definitions of type 4aMI
tive cardiac and renal effects [5–11]. Previous trials on were > 5 × 99th percentile URL cTnI increase within 48 h
whether SGLT2 inhibitors exert protective effects against of the procedure and at least one of the following: (1) evi-
renal events have been controversial [12, 13]. However, dence of prolonged ischaemia (≥ 20 min) as demonstrated
whether SGLT2 inhibitors exert myocardial and renal by prolonged chest pain; (2) ischaemic ST changes or
protective effects in patients with T2DM and chronic new pathological Q waves; (3) angiographic evidence of
coronary syndrome (CCS) undergoing percutaneous a flow-limiting complication; or (4) imaging evidence
transluminal coronary intervention (PCI) has not been of new loss of viable myocardium or new regional wall
determined. Therefore, our study aimed to explore the motion abnormality [14].
specific protective effects of dapagliflozin on the inci- We identified contrast-induced acute kidney injury
dence of cardiorenal events. (CI-AKI) events via a laboratory-based algorithm, which
identifies events on the basis of the European Society of
Methods Urogenital Radiology (ESUR) serum creatinine criteria
Study design and data sources (increase in serum creatinine levels by ≥ 44.2 µmol/L or
This was a cross-sectional analysis of patients with 0.5 mg/dL within 72 h or increase in serum creatinine lev-
T2DM and CCS undergoing PCI. Data were extracted els by ≥ 1.25 times the baseline value; hereafter referred to
from the hospital information system (HIS) of Beijing as CI-AKIESUR) [15]. As part of a sensitivity analysis, we
Hospital (a tertiary general hospital) from January 1, additionally identified inpatient episodes of acute kidney
2018, to December 31, 2021. The database included com- injury (AKI) via the Kidney Disease: Improving Global
prehensive details on admission and discharge, age, sex, Outcomes (KDIGO) serum creatinine criteria (increase
alcohol consumption, medications, interventional proce- in serum creatinine levels by ≥ 26.52 µmol/L (0.3 mg/dL)
dures, and laboratory test results of the patients. within 48 h or increase in serum creatinine levels by ≥ 1.5
times the baseline value before coronary arteriography
Patient recruitment criteria (CAG); hereafter referred to as AKIKDIGO) and recorded
The eligibility criteria included the following: inpa- the corresponding dates [16]. The final laboratory values
tients with complete datasets, age ≥ 18 years, diagno- before patients underwent CAG were used as the base-
sis of T2DM with CCS, documentation of dapagliflozin line data for analysis. This approach aimed to accurately
use > 7 days before PCI (study group) or no SGLT2 inhib- represent each patient’s baseline condition before the
itor use during PCI (control group), normal or mildly procedure. The renal functions (serum creatinine and
impaired liver function, and normal or mildly impaired urea nitrogen levels) of patients with CCS were assessed
renal function. For multiple related admissions, each upon admission and at 24, 48, and 72 h after PCI.
admission data point was recorded to avoid any omission.
The exclusion criteria were as follows: drug allergies Statistical analysis
and ketoacidosis that occurred after taking dapagliflozin; Categorical data are presented as frequencies, and they
noncoronary artery diseases that seriously affect heart were compared via the chi-square test or Fisher’s exact
function, such as moderate to severe valvular heart dis- test, as appropriate. Continuous data are reported as
ease, artificial heart valve replacement, congenital heart medians and interquartile ranges (IQRs), and they were
disease and other heart diseases; coronary artery bypass analysed via either Student’s t-test or the Mann‒Whitney
grafting; New York Heart Association cardiac function U test. Univariate and multivariate logistic regression
scale III-IV; serious diseases that affect lifespan, such as analyses were performed to determine the correlation
malignant tumours, organ failure due to various causes, between candidate variables and nonrecommended low-
severe immune system diseases, haemodynamic instabil- dose drugs. Statistical analyses were performed via the
ity, severe anaemia, and severe infections; use of drugs statistical software SPSS 26.0, and p < 0.05 was consid-
with clear cardiotoxic effects, such as anthracyclines; ered to indicate a statistically significant difference.
and incomplete information (illogical data and missing
or insufficient data). Any patient with such a history was Ethics and trial registration
excluded. The study protocol complied with the good clinical prac-
tice standards for drugs and the ethical guidelines speci-
Definition of outcome fied in the revised Declaration of Helsinki (2013). The
The primary outcomes included cardiac and renal Beijing Hospital Ethics Committee approved this study
outcomes. The cardiac outcome was periprocedural (Approval Letter Number: 2023BJYYEC-228-01), and the
Zhao et al. Cardiovascular Diabetology (2025) 24:185 Page 4 of 12

study was registered at the Chinese Clinical Trial Reg- ejection fraction was 58.00% in the dapagliflozin group
istry (Registration number: ChiCTR2300075232). Data and 58.69% in the non-SGLT2 inhibitor group.
extracted from medical records were retrospectively In this cohort study, propensity score matching (PSM)
reviewed, deidentified, and anonymized before analy- was performed to match the study group with the control
sis; therefore, the requirement for informed consent was group. Five covariates were selected for PSM: two vari-
waived for this study. ables with statistical differences at baseline, specifically
whether ARNI and GLP-1RA were used in combination
Results therapy, and three variables that showed statistical dif-
Participant characteristics ferences after the first-round PSM, namely, age, history
Among the admitted patients, 1,430 met the inclu- of hypertension, and Hgb level. These covariates were
sion criteria. A total of 176 cases and 176 controls were chosen from those presenting statistical significance
paired after propensity score matching (PSM) based on (P < 0.05) in the univariate analysis and those displaying
5 covariates. A diagram of the study process and exclu- differences after the initial PSM. The characteristics of
sion of participants is shown in Fig. 1. All the included the randomly selected participants after PSM are shown
patients had stable vital signs before PCI. Most patients in Table 2.
were asymptomatic after the operation. However, some
patients experienced symptoms such as chest pain or oli- Cardiac and renal outcomes
guria, which corresponded to PMI/4aMI and AKI in the Compared with the control group, the dapagliflozin
outcome indicators. group exhibited significantly lower rates of PMI/4aMI
The characteristics of the randomly selected partici- both pre-PSM (39.78% vs. 66.99%; OR 0.862, 95% CI
pants before PSM are shown in Table 1. The age of the 0.823–0.904; p < 0.001) and post-PSM (39.77% vs. 60.23%;
participants was 65 years (range, 59–71), and 75.66% OR 0.660, 95% CI 0.531–0.821; p < 0.001). Multivariate
of the participants were male. Both groups had similar analysis confirmed this association post-PSM (adjusted
baseline demographics, comorbidities, and laboratory OR 0.436, 95% CI 0.285–0.668; p < 0.001).
characteristics. No difference was observed in the pro- For renal outcomes, CI-AKIESUR showed a nonsig-
portions of patients with previous myocardial infarction nificant trend pre-PSM (OR 0.941, 95% CI 0.887–0.998;
(MI) (p = 0.944), previous PCI (p = 0.684), hypertension p = 0.114), which was attenuated post-PSM (OR 0.779,
(p = 0.618), or other comorbidities (p > 0.05) that might 95% CI 0.492–1.233; p = 0.358). Similarly, CI-AKIKDIGO
affect cardiac function. No differences were noted in the demonstrated no significant differences pre-PSM (OR
hypersensitive cardiac troponin I (hs-TNI) (p = 0.090), 0.963, 95% CI 0.890–1.042; p = 0.415) or post-PSM (OR
brain natriuretic peptide (BNP) (p = 0.331), creatine 0.828, 95% CI 0.494–1.390; p = 0.521). After covariate
kinase-MB (CK-MB) (p = 0.947), or serum creatinine adjustment, neither CI-AKIESUR (adjusted OR 0.561, 95%
(Scr) (p = 0.270) levels or in the estimated glomerular CI 0.161–1.953; p = 0.364) nor CI-AKIKDIGO (adjusted OR
filtration rate (eGFR) (p = 0.187), which are markers that 0.659, 95% CI 0.183–2.376; p = 0.524) achieved statistical
reflect cardiac and renal function. In terms of the base- significance.
line transthoracic echocardiogram parameters, the mean For the subgroup analysis of cardiac events, among
the populations aged ≥ 65 years, those with multivessel

Fig. 1 Flow diagram of study population enrollment

Zhao et al. Cardiovascular Diabetology (2025) 24:185 Page 5 of 12

Table 1 Basic characteristics of patients in two groups before propensity matching

DAPA user (n = 176) non-SGLT2i user (n = 1254) p value
Demographics
Female, n (%) 45 (25.57) 303 (24.16) 0.754
Age, year (IQR) 65.00 (59.75–71.00) 66.00 (59.00–72.00) 0.575
BMI, kg/m2 (IQR) 25.46 (24.04–27.73) 25.77 (23.88–28.06) 0.792
Smoking status, n (%) 92 (52.27) 651 (51.91) 0.993
Drinking status, n (%) 89 (50.57) 649 (51.75) 0.830
SBP, mmHg (IQR) 125.00 (114.00–139.00) 125.00 (114.00–136.00) 0.987
DBP, mmHg (IQR) 71.50 (65.00–78.00) 71.00 (64.00–79.00) 0.831
HR, bpm (IQR) 68.00 (64.00–72.00) 68.00 (64.00–72.00) 0.571
LVEF, % (IQR) 58.00 (58.00–64.00) 60.00 (57.00–65.00) 0.300
Comorbidities
Previous MI, n (%) 40 (22.73) 278 (22.17) 0.944
Previous PCI, n (%) 34 (19.32) 263 (20.97) 0.684
Previous CABG, n (%) 3 (1.70) 20 (1.59) 0.756
Hypertension, n (%) 127 (72.16) 931 (74.24) 0.618
AF, n (%) 13 (7.39) 77 (6.14) 0.637
HF, n (%) 11 (6.25) 92 (7.34) 0.714
Hyperlipemia, n (%) 146 (82.94) 1002 (79.90) 0.395
Ischemic stroke, n (%) 21 (11.93) 155 (12.36) 0.968
Previous cerebral hemorrhage, n (%) 0 1 (0.08) 1.000
COPD, n (%) 0 19 (1.52) 0.155
Laboratory variables
hs-TNI, pg/ml (IQR) 10.45 (5.18–21.08) 10.00 (4.20–17.80) 0.090
BNP, pg/ml (IQR) 50.49 (22.15–116.49) 53.41(24.75–118.84) 0.331
CK-MB, ng/ml (IQR) 1.90 (1.20–3.51) 1.80 (1.10–3.70) 0.947
CK, U/L (IQR) 67.50 (51.75–92.00) 76.00 (53.00–118.75) 0.131
Scr, mg/dL (IQR) 0.85 (0.70–1.01) 0.85 (0.72–1.00) 0.270
eGFR, ml/min/1.73m2 (IQR) 92.24 (77.94–107.90) 91.46 (83.35–104.97) 0.187
Ccr, mg/min (IQR) 78.34 (60.89–96.49) 76.89 (59.71–93.09) 0.293
BUN, mmol/L (IQR) 5.75 (4.85–6.47) 5.82 (4.80–6.95) 0.072
Glu, mmol/L (IQR) 6.00 (5.28–6.90) 6.10 (5.20–7.10) 0.068
HbA1c, % (IQR) 6.77 (6.20–7.20) 6.78 (6.10–7.30) 0.720
TC, mmol/L (IQR) 3.50 (2.90–4.20) 3.58 (3.06–4.14) 0.940
TG, mmol/L (IQR) 1.43 (0.99–1.70) 1.46 (1.03–1.47) 0.100
LDL-C, mmol/L (IQR) 1.87 (1.38–2.48) 1.94 (1.51–2.42) 0.704
HDL-C, mmol/L (IQR) 1.03 (0.88–1.20) 1.03 (0.96–1.11) 0.737
ALT, U/L (IQR) 16.00 (13.00–25.25) 17.00 (12.00–25.00) 0.876
AST, U/L (IQR) 18.00 (15.00–22.00) 18.00 (14.00–23.00) 0.312
GGT, U/L (IQR) 32.00 (19.75–38.00) 37.00 (22.00–38.00) 0.270
PLT, × 10⁹/L (IQR) 207.50 (175.25–242.75) 205.00 (174.00–244.00) 0.848
MYO, ng/L (IQR) 27.45 (19.48–45.45) 29.70 (21.10–49.38) 0.153
Hgb, g/L (IQR) 133.00 (122.00–144.25) 131.00 (121.00–141.00) 0.051
Description of the lesions
Single-vessel disease, n (%) 79 (44.89) 585 (46.65) 0.720
Multi-vessel disease (≥ 2), n (%) 97 (55.11) 669 (53.35) 0.720
LM lesion, n (%) 5 (2.84) 34 (2.71) 0.808
LCX lesion, n (%) 99 (56.25) 709 (56.54) 1.000
LAD lesion, n (%) 45 (25.57) 294 (23.44) 0.599
RCA lesion, n (%) 56 (31.82) 384 (30.62) 0.814
PCI information
PCI with balloon only, n(%) 91 (51.70) 640 (51.04) 0.932
PCI with stent only, n(%) 68 (38.64) 493 (39.31) 0.928
PCI with balloon and stent, n(%) 17 (9.66) 121 (9.65) 1.000
Zhao et al. Cardiovascular Diabetology (2025) 24:185 Page 6 of 12

Table 1 (continued)
DAPA user (n = 176) non-SGLT2i user (n = 1254) p value
Contrast volume, mL (IQR) 156.50 (120.00–190.00) 150.00 (130.00–185.75) 0.761
Medications
Antiplatelets, n (%) 175 (99.43) 1220 (97.29) 0.114
Anticoagulation, n (%) 2 (1.14) 21 (1.67) 1.000
β-blockers, n (%) 134 (76.14) 931 (74.24) 0.655
RAASi, n (%) 103 (58.52) 712 (56.78) 0.722
CCB, n (%) 76 (43.18) 479 (38.20) 0.235
ARNI, n (%) 39 (22.16) 147 (11.72) < 0.001
Statin, n (%) 157 (89.20) 1137 (90.67) 0.629
Ezetimibe, n (%) 67 (38.07) 492 (39.23) 0.830
Diuretic, n (%) 50 (28.41) 322 (25.68) 0.495
Metformin, n (%) 57 (32.39) 426 (33.97) 0.740
DPP-4i, n (%) 31 (17.61) 193 (15.39) 0.516
GLP-1RA, n (%) 12 (6.82) 41 (3.27) 0.034
SU, n (%) 14 (7.95) 86 (6.86) 0.707
Insulin, n (%) 51 (28.98) 286 (22.81) 0.087
Standardized hydration is not performed for patients during the peri-operative period of PCI. The type of contrast agent used in PCI is iodine contrast agent

disease, and those with high contrast agent dosages may contribute to the preservation of renal function. (4)
(≥ 150 mL), the use of dapagliflozin could better reduce An analysis of cardiac events showed that dapagliflozin
the incidence of cardiac events (Fig. 2). In terms of renal was more effective in reducing the incidence of cardiac
outcomes, subgroup analyses revealed pronounced bene- events in populations aged≥ 65 years, those with multi-
fits in patients aged ≥ 65 years, those with multivessel dis- vessel disease, and those with high contrast agent dos-
ease, and those receiving greater contrast volume (Fig. 3). ages (≥ 150 mL). To our knowledge, this is the first study
Compared with the control group, the dapagliflozin to describe data associating dapagliflozin with improved
(DAPA) group demonstrated significantly greater base- cardiac and renal outcomes among patients with T2DM
line eGFRs (91.24 vs. 87.48, p = 0.036) and post-PCI and CCSs undergoing PCI.
eGFRs (91.27 vs. 87.75, p < 0.001), indicating preserved
renal function in the DAPA-treated patients (Fig. 4). Myocardial injury protection
Previous studies have shown that SGLT2 inhibitors can
Discussion significantly increase both survival and left ventricular
Key results (LV) function in patients [17]. Research on the patho-
In this retrospective study, we compared the cardiac physiological mechanisms has shown that SGLT2 inhibi-
and renal outcomes of patients with T2DM and CCSs tors attenuate fibrosis and autophagy in border cardiac
undergoing PCI, stratified by their concomitant use of tissue in mice with MI. In Beclin1+/− and NHE1 cKO
the SGLT2 inhibitor dapagliflozin. Our analysis revealed mice, Beclin1 deficiency improved survival. Mechanisti-
three novel clinical findings. (1) Dapagliflozin signifi- cally, SGLT2 inhibitors exert a significant cardioprotec-
cantly improved cardiac outcomes. Both before and tive effect by inhibiting autophagy by targeting Beclin1
after PSM, patients in the dapagliflozin group had lower rather than NHE1. In addition, an SGLT2 inhibitor res-
PMI/4aMI rates than those in the control group. Multi- cued cardiomyocyte autosis induced by Tat-beclin1
variate analysis post-PSM further confirmed this asso- or GD, exerting cardioprotective effects by decreasing
ciation. (2) In terms of renal outcomes, dapagliflozin autophagic cell death. These findings provide new evi-
did not exert a significant effect on contrast-induced dence that SGLT2 inhibitors effectively ameliorate myo-
acute kidney injury according to the CI-AKIESUR and cardial injury in myocardial infarction by suppressing
CI-AKIKDIGO criteria, either before or after PSM, even beclin1-dependent autosis rather than effectively target-
after covariate adjustment. However, subgroup analyses ing NHE1 in cardiomyocytes [18–20].
indicated that dapagliflozin provided notable benefits in An in-hospital investigation in T2DM patients pre-
terms of renal outcomes among patients aged ≥ 65 years, senting with acute MI (AMI) who underwent PCI and
those with multivessel disease, and those receiving a high were treated with SGLT2 inhibitors revealed that the
contrast volume. (3) Compared with the control group, use of SGLT2 inhibitors was associated with a lower
the dapagliflozin group had significantly greater base- risk of major adverse cardiovascular events [21]. A
line and post-PCI eGFRs, suggesting that dapagliflozin prospective, multicentre, randomized, double-blind,
Zhao et al. Cardiovascular Diabetology (2025) 24:185 Page 7 of 12

Table 2 Basic characteristics of patients in two groups in propensity-matched dataset

DAPA group (n = 176) Control group (n = 176) p value
Demographics
Female, n (%) 45 (25.57) 37 (21.02) 0.254
Age, year (IQR) 65.00 (59.75–71.00) 66.00 (58.00–71.25) 0.827
BMI, kg/m2 (IQR) 25.46 (24.04–27.73) 26.17 (24.60–28.16) 0.179
Smoking status, n (%) 92 (52.27) 95 (53.98) 0.749
Drinking status, n (%) 89 (50.57) 98 (55.11) 0.336
SBP, mmHg (IQR) 125.00 (114.00–139.00) 124.50 (115.75–140.00) 0.619
DBP, mmHg (IQR) 71.50 (65.00–78.00) 71.00 (64.00–80.00) 0.556
HR, bpm (IQR) 68.00 (64.00–72.00) 68.00 (64.00–72.00) 0.394
LVEF, % (IQR) 58.00 (58.00–64.00) 60.00 (56.00–65.00) 0.867
Comorbidities
Previous MI, n (%) 40 (22.73) 49 (27.84) 0.270
Previous PCI, n (%) 34 (19.32) 36 (20.46) 0.789
Previous CABG, n (%) 3 (1.71) 4 (2.27) 1.000
Hypertension, n (%) 127 (72.16) 137 (77.84) 0.051
AF, n (%) 13 (7.39) 13 (7.39) 1.000
HF, n (%) 11 (6.25) 15 (8.52) 0.415
Hyperlipemia, n (%) 146 (82.96) 145 (82.39) 0.888
Ischemic stroke, n (%) 21 (11.93) 19 (10.80) 0.737
Previous cerebral hemorrhage, n (%) 0 1 (0.57) 1.000
COPD, n (%) 0 2 (1.14) 0.499
Laboratory variables
hs-TNI, pg/ml (IQR) 10.45 (5.18–21.08) 10.10 (5.30–17.83) 0.451
BNP, pg/ml (IQR) 50.49 (22.15–116.49) 57.06 (25.58–149.40) 0.127
CK-MB, ng/ml (IQR) 1.90 (1.20–3.51) 1.90 (1.20–3.53) 0.963
CK, U/L (IQR) 67.50 (51.75–92.00) 70.00 (55.00–101.00) 0.051
Scr, mg/dL (IQR) 0.85 (0.70–1.01) 0.86 (0.74–1.00) 0.135
eGFR, ml/min/1.73m2 (IQR) 91.24 (77.94–107.90) 91.27 (86.17–105.26) 0.082
Ccr, mg/min (IQR) 78.34(60.89–96.49) 76.56 (62.08–90.06) 0.346
BUN, mmol/L (IQR) 5.75 (4.85–6.47) 5.91 (4.77–6.85) 0.150
Glu, mmol/L (IQR) 6.00 (5.28–6.90) 6.10 (5.20–7.33) 0.053
HbA1c, % (IQR) 6.77 (6.20–7.20) 6.78 (6.10–7.40) 0.742
TC, mmol/L (IQR) 3.50 (2.90–4.20) 3.47 (2.99–4.22) 0.547
TG, mmol/L (IQR) 1.43 (0.99–1.70) 1.47 (1.03–1.47) 0.462
LDL-C, mmol/L (IQR) 1.87 (1.38–2.48) 1.84 (1.44–2.46) 0.425
HDL-C, mmol/L (IQR) 1.03 (0.88–1.20) 1.03 (0.98–1.12) 0.682
ALT, U/L (IQR) 16.00 (13.00–25.25) 17.50 (13.00–24.00) 0.171
AST, U/L (IQR) 18.00 (15.00–22.00) 18.00 (14.00–24.00) 0.126
GGT, U/L (IQR) 32.00 (19.75–38.00) 36.00 (24.00–38.00) 0.155
PLT, × 109/L (IQR) 207.50 (175.25–242.75) 205.50 (174.75–244.25) 0.667
MYO, ng/L (IQR) 27.45 (19.48–45.45) 30.30 (21.38–49.48) 0.123
Hgb, g/L (IQR) 133.00 (122.00–144.25) 133.00 (121.75–143.00) 0.637
Description of the lesions
Single-vessel disease, n (%) 79 (44.89) 93 (52.84) 0.135
Multi-vessel disease (≥ 2), n (%) 97 (55.11) 83 (47.16) 0.135
LM lesion, n (%) 5 (2.84) 4 (2.27) 1.000
LCX lesion, n (%) 99 (56.25) 103 (58.52) 0.666
LAD lesion, n (%) 45 (25.57) 38 (21.59) 0.379
RCA lesion, n (%) 56 (31.82) 52 (29.55) 0.644
PCI information
PCI with balloon only, n (%) 91 (51.71) 84 (47.73) 0.456
PCI with stent only, n (%) 68 (38.64) 75 (42.62) 0.447
PCI with balloon and stent, n (%) 17 (9.66) 17 (9.66) 1.000
Zhao et al. Cardiovascular Diabetology (2025) 24:185 Page 8 of 12

Table 2 (continued)
DAPA group (n = 176) Control group (n = 176) p value
Contrast volume, mL (IQR) 156.50 (120.00–190.00) 152.50 (135.00–190.00) 0.778
Medications
Antiplatelets, n (%) 175 (99.43) 172 (97.73) 0.371
Anticoagulation, n (%) 2 (1.14) 4 (2.27) 0.685
β-blockers, n (%) 134 (76.14) 136 (77.27) 0.801
RAASi, n (%) 103 (58.52) 113 (64.21) 0.274
CCB, n (%) 76 (43.18) 80 (45.46) 0.668
ARNI, n (%) 39 (22.16) 39 (22.16) 1.000
Statin, n (%) 157 (89.21) 162 (92.05) 0.361
Ezetimibe, n (%) 67 (38.07) 70 (39.77) 0.743
Diuretic, n (%) 50 (28.41) 53 (30.11) 0.725
Metformin, n (%) 57 (32.39) 47 (26.71) 0.243
DPP-4i, n (%) 31 (17.61) 34 (19.32) 0.680
GLP-1RA, n (%) 12 (6.82) 12 (6.82) 1.000
SU, n (%) 14 (7.96) 13 (7.39) 0.841
Insulin, n (%) 51 (28.98) 43 (24.43) 0.335

placebo-controlled trial analysed whether SGLT2 inhibi- the multivessel lesion subgroup. A larger dosage of con-
tor treatment initiated within 72 h following PCI in trast agent may suggest a longer PCI time, more diseased
patients with or without diabetes mellitus would result in blood vessels, and more complex PCI procedures.
a decrease in N-terminal prohormone of brain natriuretic In the subgroup analysis, we also included whether
peptide (NT-proBNP) levels. The results revealed that in DPP4 inhibitors or GLP-1 receptor agonists were used
patients with a recent MI, SGLT2 inhibitors were associ- in combination because these two types of drugs are cur-
ated with substantially increased NT-proBNP levels [22]. rently known to have cardioprotective effects. We did this
According to the 4th Universal Definition of Myo- to rule out the confounding factors of combined medica-
cardial Infarction, MI associated with PCI is catego- tions that might affect the results. However, based on the
rized as type 4aMI, which is primarily determined by results of this study, the combined use of medications did
the elevation level of cTnI [23]. Numerous studies have not have an effect on the outcomes.
demonstrated that the PMI is related to the subsequent
increased risk of mortality and other adverse cardiovas- Renal injury protection
cular events [24]. Therefore, we chose the PMI/4aMI as PCI is a widely used treatment for patients with coronary
our cardiac outcome indicator, which could better reflect heart disease. Intra-arterial administration of iodinated
myocardial damage during PCI. To our knowledge, our contrast media during PCI may induce renal impairment
study is the first trial in which PMI/4aMI was used to [25–27]. CI-AKI is a substantial concern following expo-
assess cardiac and myocardial impairment outcomes. sure to iodinated contrast media that are used in diag-
Consistent with previous results, our study revealed nostic or interventional procedures and may represent a
that dapagliflozin obviously improved cardiac outcomes. significant cause of iatrogenic renal dysfunction, contrib-
Initiating dapagliflozin more than 1 week before PCI in uting to adverse clinical outcomes [25, 26].
patients with T2DM and CCS could significantly reduce Several clinical trials have consistently indicated that
PMI/4aMI events compared with no use of SGLT2 inhib- the use of an SGLT2 inhibitor can provide renal protec-
itors. Our results indicate that early dapagliflozin intake tion through a decreased rate of decline in the eGFR
before PCI (more than 1 week) may be associated with and reduced onset or progression of albuminuria [28].
improved cardiovascular benefits. According to previous experiments, the pathophysiologi-
The results of the forest plots in the subgroup analysis cal mechanisms underlying the renoprotective effects
of this study revealed that, for people aged 65 and above, of SGLT2 inhibitors include the following: (1) osmotic
the use of dapagliflozin before PCI had a more signifi- diuresis, natriuretic and hypovolaemia [29–31]; (2) tubu-
cant myocardial protective effect. In addition, in patients loglomerular feedback [32–34]; (3) tubular oxygenation
with multivessel lesions, the use of dapagliflozin pro- [35–37]; (4) tubular energetics and sodium‒hydrogen
vides better myocardial protection. The subgroup analy- exchange [36–38]; and (5) inflammation and fibrosis [39].
sis also revealed that in the subgroup with a high dose of Several other mechanisms are considered to contribute
contrast agent, the protective effect of dapagliflozin was to the renoprotective effect of SGLT2 inhibition [40].
more obvious, and this result was consistent with that of
Zhao et al. Cardiovascular Diabetology (2025) 24:185 Page 9 of 12

Fig. 2 Subgroup analyses for cardiac events (PIM/4aMI). DCB: drug-coated balloon; DES: drug-eluting stent

Previous studies that examined the real-world risk of significant difference between the dapagliflozin group
CI-AKI in patients who received SGLT2 inhibitors dur- and the control group. The results of the subgroup for-
ing PCI did not identify an association between CI-AKI est plot analysis revealed pronounced benefits in patients
reduction and the use of SGLT2 inhibitors [25]. In con- aged≥ 65 years, those with multivessel disease, and those
trast, other trials confirmed the benefit of SGLT2 inhibi- receiving greater contrast volume.
tors in protecting against CI-AKI [21, 41]. A multicentre Considering that CI-AKI is a relatively strict indicator
international registry trial revealed that the use of SGLT2 that is used to evaluated renal injury and that eGFR can
inhibitors was associated with a significantly lower occur- more sensitively reflect the trend of change in patients'
rence of CI-AKI in patients with T2DM and AMI [21]. renal function, we conducted a paired analysis of the
In this study, for the two renal event outcomes of CI- changes in eGFR before and after PCI in the two groups.
AKIEUSR and CI-AKIKDIGO, neither the univariate analy- The results showed that the dapagliflozin group had
sis nor the multivariate regression analysis revealed a
Zhao et al. Cardiovascular Diabetology (2025) 24:185 Page 10 of 12

Fig. 3 Subgroup analyses for cardiac events (CI-AKIESUR and CI-AKIKDIGO)

Fig. 4 Box plot and line plot comparing the distribution of the eGFR before and after PCI in the DAPA group vs. the control group
Zhao et al. Cardiovascular Diabetology (2025) 24:185 Page 11 of 12

the data. Zinan ZHAO wrote the manuscript. Deping LIU, Tianqi ZHANG, and
better performance in terms of eGFR reduction before Zinan ZHAO participated in the discussion of the results. All the authors have
and after PCI than did the control group. read and approved the final manuscript.
Currently available measures, such as the eGFR, are
Fundings
sensitive indicators that help in the early identification This work was financially supported by National High Level Hospital Clinical
of renal impairment [42]. Hence, we chose the eGFR and Research Funding (Nos. BJ-2023-081, BJ-2023-199). Role of the Funder/
CI-AKI to evaluate renal injury. To our knowledge, this Sponsor: The funding sources had no role in the design and conduct of
the study; collection, management, analysis, and interpretation of the data;
is the first trial employing both the eGFR and two dis- preparation, review, or approval of themanuscript; and the decision to submit
tinct criteria for CI-AKI as renal outcomes. Our results the manuscript for publication.
showed that dapagliflozin initiation more than 1 week
Availability of data and materials
before PCI was associated with a decrease in the eGFR. All data relevant to the study are included in the art icle or uploaded
No significant reduction in CI-AKI events was detected assupplementary information.
in patients treated with dapagliflozin compared with con-
trols. These results suggest that dapagliflozin could pro- Declarations
tect against early renal injury in patients with T2DM and
Consent for publication
CCS undergoing PCI. All the authors provided consent for publication.

Study limitations Comepting interests

The authors declare that the research was conducted in the absence of any
Our results should be interpreted in light of several limi- commercialor financial relationships.
tations. This was a retrospective study based on a mod-
erately sized cohort from a single centre; thus, sampling Author details
1
Department of Pharmacy, Beijing Hospital, National Center of
bias is possible because of the retrospective nature of Gerontology; Institute of Geriatric Medicine, Chinese Academy of Medical
the data. Moreover, because of the limited number of Sciences; Beijing Key Laboratory of Assessment of Clinical Drugs Risk
patients enrolled, an assessment of specific outcome and Individual Application (Beijing Hospital), Beijing, People’s Republic of
China
measures and subgroup analysis could not be conducted. 2
Department of Cardiology, Beijing Hospital, National Center of
Third, long-term outcomes were not evaluated. Larger Gerontology; Institute of Geriatric Medicine, Chinese Academy of Medical
cohorts and multicentre studies are necessary to further Sciences, Beijing, People’s Republic of China
3
The Key Laboratory of Geriatrics, Beijing Institute of Geriatrics, Institute
assess the potential protective effects of dapagliflozin of Geriatric Medicine, Chinese Academy of Medical Sciences, Beijing
on the risk of myocardial and kidney damage in patients Hospital/National Center of Gerontology of National Health Commission,
with T2DM and CCS undergoing PCI. Beijing, People’s Republic of China

Received: 2 November 2024 / Accepted: 8 March 2025

Conclusions
This cohort study demonstrated that dapagliflozin sig-
nificantly reduces the rates of PMI/4aMI before and
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