Differential Outcomes With Empagliflozin and Dapagliflozin in Heart Failure With Mildly Reduced Ejection Fraction With and Without Diabetes Mellitus

Sodium?glucose cotransporter-2 (SGLT2) inhibitors improve outcomes in heart failure (HF), yet comparative effectiveness between individual agents in heart failure with mildly reduced ejection fraction (HFmrEF) remains limited. We conducted a retrospective cohort study using the TriNetX Global Collaborative Network electronic health record database. Adults (≥18 years) with HF and left ventricular ejection fraction (LVEF) 41% to 49% initiating empagliflozin or dapagliflozin between September 1, 2021, and September 1, 2022, were included. Propensity score matching (1:1) balanced demographics, comorbidities, medications, and laboratory values, yielding 1,386 patients per group. Outcomes were assessed over 1 year after treatment initiation and included all-cause mortality, hospitalization, HF exacerbation, and urinary tract infection (UTI). Risk analyses and Kaplan?Meier survival analyses with hazard ratios (HRs) were performed. In the matched cohort, empagliflozin was associated with significantly lower hazards of hospitalization (HR 0.54, 95% CI 0.49 to 0.60), HF exacerbation (HR 0.63, 95% CI 0.55 to 0.71), and UTI (HR 0.70, 95% CI 0.55 to 0.90) compared with dapagliflozin. All-cause mortality was numerically lower with empagliflozin but did not reach statistical significance (HR 0.86, 95% CI 0.67 to 1.10). In conclusion, in this large real-world HFmrEF population, empagliflozin was associated with lower hazards of hospitalization, HF exacerbation, and UTI compared with dapagliflozin, with no significant difference in mortality. These findings suggest potential heterogeneity in clinical effectiveness among SGLT2 inhibitors in HFmrEF and warrant confirmation in prospective comparative studies.