Effect of Sodium-Glucose Cotransporter Type 2 Inhibitors on Clinical Outcomes in Patients With Cardiovascular Disease: A Meta-Analysis of Randomized Controlled Trials

Abstract

BackgroundControlled studies and observational studies have shown that sodium-glucose cotransporter type 2 inhibitors (SGLT-2s) are beneficial to the mortality of patients with heart failure (HF). However, it is unclear whether SGLT-2s can benefit patients with other cardiovascular diseases. Here, we conducted a systematic review and meta-analysis to determine the clinical benefits of SGLT-2s in cardiovascular patients with or without diabetes.MethodsWe searched PubMed, EMBASE, Cochrane Library, Web of Science databases, and ClinicalTrials.gov databases for randomised controlled trials written in English from inception until November 1, 2020. Two reviewers independently identified randomised controlled trials comparing the effects of SGLT-2s in patients with cardiovascular disease with or without diabetes. Primary outcomes were all-cause mortality, cardiovascular mortality, and hospitalisation for heart failure. Secondary outcomes were major adverse events from cardiovascular, metabolic, renal, and infectious diseases. The effects of SGLT-2s were evaluated using RevMan5.3 software. The Cochrane risk of bias tool was used to assess study quality.ResultsWe identified 10 randomised controlled trials (24500 patients in the SGLT-2 group and 17960 patients in the placebo group). Meta-analysis showed that SGLT-2 treatment significantly reduced all-cause mortality, cardiovascular mortality, and hospitalisation for heart failure (HHF) in patients with cardiovascular disease (all-cause mortality relative risk [RR]: 0.86; 95% confidence interval [CI]: 0.80–0.91; P < 0.00001; I2 = 11%; cardiovascular mortality RR: 0.85; 95% CI: 0.79–0.92; P < 0.0001; I2 = 35%; HHF RR: 0.69; 95% CI: 0.64–0.81; P < 0.00001; I2 = 0%). In patients with heart failure, mortality and HHF after SGLT-2 treatment for heart failure with reduced ejection fraction were significantly reduced, whereas heart failure with preserved ejection fraction did not differ compared with placebo treatment. Moreover, SGLT-2s induced a lower incidence of renal damage and myocardial infarction than the placebo group; however, the risk of infection, amputation, volume depletion, and diabetic ketoacidosis was higher. ConclusionsIn this exploratory analysis, SGLT-2s had significant clinical effects in the treatment of patients with cardiovascular disease and had significant benefits in terms of renal function and myocardial infarction, but were associated with increased risk of infection, ketoacidosis, amputation, and volume depletion.