Table 1.
General Characteristics of Included Studies.
| Study, year, country | Design | Participants | Exposition | Outcome | Adjustment factors | OR/RR/HR (95% CI) |
|---|---|---|---|---|---|---|
| Paolisso P et al. (22) 2022, multicenter (Europe). The SGLT2I AMI PROTECT Registry. | PCS | AMI patients with diabetes undergoing PCI between 2018 and 2021. N = 646 AMI patients (with or without ST-segment elevation): 111 SGLT2Is users and 535 non-SGLT2Is users. Follow-up of 24 ± 13 months. The mean age of the overall population was 70 [61–79] years, and >77% were males. Exclusion criteria: patients on insulin therapy or with incomplete information on medical therapy, CABG, severe valvular HD, prosthetic heart valves, severe anemia, history of bleeding, pulmonary embolism, GFR <30 ml/min/1.73 m2, malignancies, and follow-up data shorter than 3 months. SGLT2I patients were younger (p < 0.001) and had better renal function at admission compared to non-SGLT2-I users (p = 0.886). | SGLT2Is users (started at least 3 months before hospitalization) vs. non-SGLT2Is users (if patients received other OAD strategies). The type and dose of SLGT2i are not specified. The sample size was powered to evaluate only a “class effect” but not the “doses effect.” The mean time of SGLT2I therapy duration was 7.3 ± 3 months. No explicit detail is provided if the SGLT2Is were suspended before the procedure and if this was the case, when they were restarted. | Primary endpoint: a composite of CV death, recurrent AMI, and hospitalization for HF (MACE). Secondary outcomes: i) in-hospital CV death, recurrent AMI, occurrence of arrhythmias, and CIN; ii) long-term CV mortality, recurrent AMI, and HF hospitalization. No definition of CIN is provided. | Not described for renal outcomes. | The use of SGLT2Is was an independent predictor of reduced risk of MACE (aHR = 0.57; 95% CI 0.33–0.99; p = 0.039) and HF hospitalization (aHR = 0.46; 95% CI 0.21–0.98; p = 0.041). CIN: among SGLT2Is users 6/111, 70/535 among non-SGLT2-I users (p = 0.022). Crude RR 0.4131; 95% CI 0.1841-0.9271. |
| Paolisso P et al. (23) 2023, multicenter (Europe). The SGLT2I AMI PROTECT Registry. | The development of CIN in patients with diabetes and AMI undergoing PCI. No definition of CIN is provided. | CKD and anti-diabetic therapy at admission (SGLT2Is vs. non-SGLT2Is users). | The use of SGLT2Is was an independent predictor of reduced rate of CIN (aOR 0.356; 95% CI 0.134–0.943, p = 0.038). | |||
| Hua R et al. (24) 2022, China | RCS | Patients with T2D undergoing PCI between January 1, 2020 and December 30, 2021. Before propensity score matching analysis: 245 in the SGLT2Is cohort and 1,265 in the non-user cohort. After matching: 242 SGLT2Is users and 242 non-users. Age: users 62.6 (55–63) and non-users 63.6 (57–71) years. Female: users 37 (30.5) and non-users 36 (29.8). Mean follow-up was not reported. Compared with non-users, SGLT2 inhibitor users tended to be at a lower age (p < 0.01), with significantly lower comorbidities, namely, HF (p < 0.01) and PCI history (p < 0.01), compared with SGLT2 inhibitor non-users. They also had higher eGFR (p = 0.0154) and a higher proportion of metformin use (p < 0.01) compared with non-users. |
The exposure of interest was a prescription of an SGLT2I, including canagliflozin, empagliflozin, or dapagliflozin, for at least 6 months till the date of PCI. SGLT2Is types used: dapagliflozin 172 (71.1%), empagliflozin 41 (16.9%), canagliflozin 29 (12.0%). The dose of the SGLT2I is not specified. No explicit detail is provided if the SGLT2Is were stopped prior to the procedure and if this was the case, when they were restarted. | The risk of CIN in SGLT2I users undergoing PCI. The definition of CIN was based on the ESUR and KDIGO criteria. Evaluation of renal function indicators in users and non-users was performed at 24, 48, and 72 h post-PCI. | Age, sex, PCI history, NYHA ≥ III, and metformin use. | For CIN among users compared to non-users aOR 0.37; 95% CI 0.19–0.67; p < 0.01. CIN events: 13/245 in the SGLT2i user cohort and 121/1,265 in the non-user cohort (before propensity matching analysis). Age (aOR 1.06, 95% CI 1.02–1.11), PCI history (aOR 7.84, 95% CI 3.26–18.84), and NYHA grade ≥ III (aOR 7.92, 95% CI 1.80–34.91) were independent risk factors of CI-AKI for patients undergoing PCI. |
| Özkan U et (25). 2023, Turky | CCS | N = 312 patients with diabetes who underwent CAG and/or PCI between January 1 2020 and July 1 2022: 104 T2D patients using SGLT2Is and 208 T2D patients as a control group. The median age was 59.5 years (45–80) and 189 (60.6%) were male. Mean follow-up was not reported. Exclusion criteria: patients with active infection (including COVID-19), patients with CHF (EF < 40%), patients with malignancy, patients with autoimmune disease, patients using chronic anti-inflammatory drugs, patients with severe anemia, patients with eGFR < 30 mL/min/1.73 m2, patients who used nephrotoxic agents, patients with cardiogenic shock, and patients with a previous history of CIN. There were no differences between the treatment groups regarding sex (p = 0.54), age (p = 0.49) or preprocedural serum creatinine (p = 0.13) or eGFR (p = 0.28). | Patients who used SGLT2Is in the T2D treatment regimen before CAG and/or PCI were included in the study. The type and dose of SGLT2Is are not specified. The administration time of GLT2I prior to the procedure is not detailed. No explicit detail is provided if the SGLT2Is were stopped prior to the procedure and if this was the case, when they were restarted. | Diagnosis of CIN: a 0.5 mg/dL or 25% increase in SCr levels within 48 h, an increase in SCr of ≥ 1.5 times the baseline within 7 days, or a urinary output of < 0.5 mL/kg/h for at least 6 h after using the contrast agent compared to its level before the procedure (CAG and/or PCI). The values of SCr levels were measured before the procedure and 48–72 hours after that. | Age, sex, HT, smoking, prior revascularization, contrast volume, drinking, glucose, HbA1c, LVEF%, different medications, etc. | CIN: among no previous SGLT2Is users 64/208 and previous SGLT2Is users 14/104. SGLT2 inhibitors significantly reduced the risk of CIN aOR 0.41; 95% CI 0.142–0.966, p = 0.004. |
| Bernardini F et al. (27) 2022, Italy | RCS | N = 408 T2D patients undergoing PCI divided into three groups: 136 treated with new-antidiabetic drugs, 136 treated with standard-antidiabetic therapy, and 136 patients without diabetes. Mean follow-up was not reported. Exclusion criteria: not reported. The patients treated with SGLT2Is presented pre-PCI mean creatinine levels significantly lower (0.83 ± 0.16 mg/dL) than those treated with DPP-4 inhibitors (1.04 ± 0.34 mg/dL) and GLP-1 analogues (1.05 ± 0.39 mg/dL), (p for trend = 0.009). | New drugs: GLP-1 analogues, DPP-4 inhibitors, SGLT2Is. Standard therapy: metformin, sulfonylureas, thiazolidinediones, insulin. The type, dose, the administration time of SGLT2I prior to the procedure is not detailed. No explicit detail is provided if the SGLT2Is were suspended before the procedure and if this was the case, when they were restarted. | CIN was defined as an increase in SCr levels ≥ 0.3 mg/dL or > 25% of the base value, which occurred 24-48 hours after administration of the contrast medium. SCr level was measured at the time of hospitalization, 24-hour and 48-hour post-PCI. | None. | The incidence of CIN was 5.1% in the standard-antidiabetic therapy group, 3.8% in the new-antidiabetic drugs group, and 2.9% in patients without diabetes (p = 0.911). Crude RR 0.7143; 95% CI 0.2324-2.1953. |
| Santos-Gallego CG et al. (26) 2020, USA | RCS | Patients with diabetes who underwent PCI between January 2016 and May 2017. Patients with diabetes taking chronic SGLT2Is preadmission compared with age- and gender-matched patients with diabetes not taking SGLT2Is. Mean follow-up was not reported. Exclusion criteria: not reported. There was no difference in both groups in clinical characteristics (CVRF previous revascularization, HbA1c, LVEF, prior medical treatment), preprocedural analysis (serum creatinine, eGFR, BNP), or procedural characteristics (contrast volume, number of stents, LVEDP). | SGLT2Is users vs. non-SGLT2Is users matched by age and sex. The type, dose, the administration time of SGLT2I prior to the procedure is not detailed. No explicit detail is provided if the SGLT2Is were suspended prior to the procedure and if this was the case, when they were restarted. |
CIN was defined as an increase in SCr higher than 30% or higher than 0.3 mg/dL one-day post-PCI | None. | Less SGLT2i users developed CIN (3.8 vs 17.3%, p<0.05) compared to non-users. Crude RR 0.2222; 95% CI 0.0504-0.9793. |
| Feitosa MPM et al. (28) 2023, Brasil. SAFE-PCI trial: a pilot, single-center, open-label RCT. | RCT | Patients with T2D undergoing elective PCI. Follow−up of 30 days. N = 42 patients (22 patients in the SGLT2Is group and 20 patients in the control group). The mean age among SGLT2Is users and control group were 65 ± 10 and 64 ± 6 years, respectively. Exclusion criteria: eGFR < 30 mL/min/1.73m2 or dialysis therapy, ACS in the last 30 days, need for urgent or emergency PCI, use of NSAID in the last 30 days before randomization; known pregnancy; and inability to sign the consent form. There were no differences between the treatment groups regarding sex (p = 0.42), age (p = 0.82), preprocedural serum creatinine (p = 0.24), urea (p = 0.64) or eGFR (p = 0.10). | SGLT2Is (empagliflozin 25 mg/d initiated at least 15 days before PCI and maintained until the end of the follow−up period) vs. placebo. SGLT2Is were continued throughout the follow-up period, including the day of the procedure. | CIN up to 48 h after PCI. Definition of CIN, according to KDIGO criteria. | Not described. | The incidence of CIN was similar in both groups: in 3 patients in the SGLT2Is group (13.6%) and 2 patients in the control group (10%) (p = 0.71). Crude RR 0.9680; 95% CI 0.7957-1.1776. |
MC-CS, multi-center prospective cohort study; PCI, percutaneous coronary intervention; CABG, coronary artery bypass graft surgery; CAG, coronary arteriography; CHF, congestive heart failure; EF, ejection fraction; CV, cardiovascular; CVRF, cardiovascular risk factor; AMI, acute myocardial infarction; MACE, major CV events; AKI, acute kidney injury; CIN, contrast-induced nephropathy; CKD, chronic kidney disease; HF, heart failure; NSTEMI, non-ST segment Elevation Myocardial Infarction; CRP, C-reactive Protein; CyC, Cystatin C; HD, heart disease; Hs-TnI, high sensitivity Troponin I; MR, mitral regurgitation; GFR, glomerular filtration rate; eGFR, estimated GFR; ESUR, European Society of Urogenital Radiology; KDIGO, Kidney Disease, Improving Global Outcomes; PCS, prospective cohort study; RCS, retrospective cohort study; CCS, case-control study; RCT, randomized controlled trial; NYHA, New York Heart Association; T2D, type 2 diabetes mellitus; SGLT2I, SGLT2 inhibitor; oGLDs, other glucose-lowering drugs; NGAL, Neutrophil Gelatinase−associated Lipocalin; HbA1c, glycated hemoglobin; LVEF, left ventricle ejection fraction; LVEDP, Left ventricular end-diastolic pressure; SCr, serum creatinine; OAD, oral anti-diabetic agent; BNP, brain natriuretic peptide; ACS, acute coronary syndrome; NSAID, non-steroidal anti-inflammatory drugs.