Comparative efficacy of dapagliflozin and empagliflozin on hospitalization for heart failure and cardiovascular death in patients with heart failure with preserved ejection fraction: a network meta-analysis

Introduction: Heart Failure with Preserved Ejection Fraction (HFpEF) is a complex syndrome with increasing prevalence, especially among older populations with hypertension and diabetes. Despite similar mortality rates to heart failure with reduced ejection fraction (HFrEF), HFpEF remains difficult to manage due to limited effective treatments. Recent studies have highlighted the benefits of Sodium-Glucose Cotransporter 2 (SGLT2) inhibitors, like dapagliflozin and empagliflozin, in improving outcomes in HFpEF. This meta-analysis aims to compare the efficacy of these two agents in reducing heart failure hospitalization and cardiovascular death. Methods: This meta-analysis followed preferred reporting items for systematic reviews and meta-analyses (PRISMA) 2020 guidelines. Relevant studies were identified through systematic searches in PubMed, Cochrane Library, and ScienceDirect using specific keywords. Eligible randomized controlled trials evaluating dapagliflozin and empagliflozin in HFpEF patients were included. Risk of bias was assessed using the Cochrane RoB2 Tool, and statistical analysis was conducted using a random effects model. Results: Six phase III randomized controlled trials (RCTs) involving 36,478 participants (mean age ~71 years) were included. The studies, conducted across over 20 countries, compared empagliflozin and dapagliflozin to placebo in HFpEF patients. Empagliflozin showed the highest probability of reducing heart failure hospitalization (SUCRA 0.875) and cardiovascular death (SUCRA 0.78), outperforming dapagliflozin (SUCRA 0.625 and 0.65, respectively). Both SGLT2 inhibitors significantly reduced hospitalization and cardiovascular death compared to placebo, with empagliflozin demonstrating the most favorable outcomes in both measures. Rank probability plots confirmed empagliflozin as the most effective treatment. Conclusion: Empagliflozin outperforms dapagliflozin in reducing heart failure hospitalization and cardiovascular death in HFpEF patients, demonstrating superior efficacy compared to placebo in multiple clinical outcomes.