Efficacy and Safety of Dapagliflozin in Patients with Heart Failure and Mildly Reduced or Preserved Ejection Fractions: A Systematic Review and Meta-Analysis

Abstract

Introduction: Dapagliflozin, an SGLT2 inhibitor, has shown benefits in heart failure. This meta-analysis evaluates its efficacy and safety in patients with heart failure with mildly reduced or preserved ejection fraction (HFmrEF or HFpEF).

Methods: PubMed, Cochrane, and Web of Science were searched for studies published between 2019 and 2024. Six randomized trials involving 8,651 patients with ejection fraction >40% were included. Primary outcomes were heart failure hospitalization and mortality. Safety outcomes included adverse events. Pooled risk ratios (RR) with 95% confidence intervals (CI) were calculated. The review is registered with PROSPERO (CRD420261307461).

Results: Dapagliflozin reduced heart failure hospitalizations by 21% (RR0.79, 95% CI 0.69–0.89, p=0.0002). Reductions in all-cause mortality (RR 0.95, 95% CI 0.86–1.06, p=0.35) and cardiovascular death (RR0.94, 95% CI 0.81–1.10, p=0.48) were not significant; moderate heterogeneity was observed for cardiovascular death (I²=66%). Dapagliflozin was not associated with significant increases in serious adverse events (RR0.96, 95% CI 0.91–1.01), volume depletion (RR1.36, 95% CI 0.91–2.02), acute kidney injury (RR0.94, 95% CI 0.82–1.08), or hypoglycaemia (RR0.98, 95% CI 0.35–2.74).

Conclusion: Dapagliflozin reduces heart failure hospitalizations in HFpEF and HFmrEF patients without significant adverse effects. Careful monitoring for volume depletion is advised. Further studies are needed on mortality.