Sodium-Glucose Cotransporter-2 Inhibitors in Heart Failure: A Meta-Analysis of Randomized Clinical Trials

Background: We aimed to conduct this study with the goal of further clarifying the role of sodium-glucose cotransporter-2 inhibitors (SGLT2i) in patients with preexisting heart failure with reduced ejection fraction with or without diabetes and to leverage increased sample size and power to evaluate clinically important secondary safety and efficacy outcomes. Methods: This meta-analysis was completed according to Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. The primary outcome was a composite of cardiovascular death or heart failure hospitalization. Secondary outcomes included the individual components of the primary outcome; major adverse cardiovascular events (defined as a composite of cardiovascular death, myocardial infarction, stroke), any death, myocardial infarction, or stroke, along with adverse events such as volume depletion, acute kidney injury, adverse events leading to drug discontinuation, amputation, and severe hypoglycemia. Other outcomes included the Kansas City Cardiomyopathy Questionnaire (KCCQ) total symptom score and changes in N-terminal pro-hormone BNP (NT-proBNP). Pooled hazard ratios (HRs) and 95% confidence intervals (CIs) for dichotomous variables and weighted difference (MD) and 95% CI for continuous variables. Results: Compared with placebo, SGLT2i use was associated with a significant reduction of cardiovascular death or heart failure hospitalization (HR = 0.74; 95% CI = 0.66-0.82; P <0.01), heart failure hospitalization (HR = 0.69; 95% CI = 0.57-0.84; P <0.01), cardiovascular death (HR = 0.79; 95% CI = 0.68-0.92; P <0.01), and any death (HR = 0.80; 95% CI = 0.70-0.92; P <0.01). Conclusions: SGLT2i was associated with a decreased risk of clinically relevant cardiovascular death, heart failure hospitalization, and heart failure symptoms with similar rates of adverse events.