Empagliflozin in Patients With Heart Failure: A Systematic Review and Meta-Analysis of Randomized Controlled Trials

Purpose: The purpose of the study is to evaluate the effect of empagliflozin in patients with heart failure (HF). Method: We performed a systematic search of PubMed, EMBASE, and the Cochrane Library database through January 20, 2021. Randomized controlled trials (RCTs) were included that compared empagliflozin and placebo in patients with HF. Dichotomous variables were expressed as risk ratios (RRs) with 95% confidence intervals (CIs). Continuous variables were calculated and expressed as mean differences (MD) and standard deviation (SD). Meta-analysis was conducted using a random-effects model on outcomes with high heterogeneity. Results: Seven studies were included in our meta-analysis (n = 5,150). Significant differences were observed in a composite of cardiovascular death or hospitalization for worsening heart failure [RR: 0.77 (95% CI 0.68–0.87); I(2) = 18%; P < 0.0001), hospitalization for worsening heart failure [RR: 0.71 (95% CI 0.61–0.82); I(2) = 0%; P < 0.00001], changes in Kansas City Cardiomyopathy Questionnaire (KCCQ) score [MD: 1.70 (95% CI 1.67–1.73); I(2) = 0%; P < 0.00001], and changes in body weight [MD: −1.43 (95% CI −2.15 to −0.72); I(2) = 84%; P < 0.0001) from baseline. However, empagliflozin did not show a better change in the 6-min walk test (6MWT) [MD: 34.06 (95% CI −29.75–97.88); I(2) = 97%; P = 0.30] or NT-proBNP [MD: −98.36 (95% CI, −225.83–29.11); I(2) = 68%; P = 0.13] from baseline. Conclusion: The findings suggest that empagliflozin was effective in reducing a composite of cardiovascular death or hospitalization for worsening heart failure. Further well-designed RCTs are needed to evaluate the long-term effect of empagliflozin in patients with HF. PROSPERO: CRD42021231712.