Empagliflozin Provides Greater Protection Against Atrial Fibrillation Than Dapagliflozin in HFpEF

Abstract 2304101, presented at Western Atrial Fibrillation Symposium 2026

Heart failure with preserved ejection fraction (HFpEF) and atrial fibrillation (AF) frequently coexist and mutually worsen disease progression. Although sodium-glucose cotransporter-2 (SGLT2) inhibitors are recommended as class IA therapy in the European Society of Cardiology (ESC) guidelines for HFpEF, it is unclear whether individual agents within this class differ in their ability to reduce AF risk or improve cardiovascular outcomes. Therefore, we assessed for differences in AF risk and cardiovascular outcomes between empagliflozin and dapagliflozin among patients with HFpEF.We conducted a retrospective cohort analysis using the TriNetX global federated health research network including 148 health care organizations. Patients diagnosed with HFpEF (ICD-10: I50.30) who were started empagliflozin or dapagliflozin were included. Propensity-score matching (1:1) on demographics, comorbidities, and cardiovascular medications resulted in two balanced cohorts of 56,025 patients. Relative risk (RR) was used to compare overall event incidence. Kaplan-Meier analyses with hazard ratios (HR) were used to evaluate time-to-event outcomes over a median follow-up of 353 days.AF incidence was similar between empagliflozin and dapagliflozin (RR 0.97; p = 0.24). However, empagliflozin was associated with a reduced risk of myocardial infarction (MI) (RR 0.87; 95% CI 0.83-0.92; p < 0.001), with no significant differences in all-cause mortality (RR 0.976; p = 0.12), stroke (RR 1.009; p = 0.79), or hospitalization (RR 1.03; p = 0.126). Moreover, empagliflozin significantly delayed the onset of AF (HR 0.91; 95% CI 0.86-0.96; p = 0.001), MI (HR 0.84; 95% CI 0.80-0.89; p < 0.001), and all-cause mortality (HR 0.93; 95% CI 0.90-0.96; p < 0.001) compared to dapagliflozin.Although the overall incidence of major outcomes was similar, empagliflozin significantly delayed the occurrence of AF, MI, and death compared with dapagliflozin. These results suggest that empagliflozin may confer earlier cardioprotective benefits, despite both agents being class IA therapies for HFpEF. Prospective studies and randomized trials are needed to determine whether these differences should guide clinical decision.