Empagliflozin versus dapagliflozin in heart failure

Abstract Background No clinical trial has compared head-to-head the effects of empagliflozin and dapagliflozin in patients with heart failure. Purpose To compare the risk of heart failure rehospitalization or all-cause death between initiators of empagliflozin and dapagliflozin in patients with heart failure. Methods This new-user, active-comparator cohort study used nationwide Danish healthcare data to emulate a hypothetical target trial that would compare the risk of heart failure rehospitalization or all-cause death in adults with heart failure initiating empagliflozin (intervention) or dapagliflozin (comparator) (Figure 1). Patients were identified from the Danish Heart Failure Registry, which enrolls patients at their first-time hospital contact with heart failure, meeting the European Society of Cardiology criteria. The primary outcome was a composite of heart failure rehospitalization and all-cause death, while secondary outcomes included each component separately. Heart failure rehospitalization was identified from the Danish National Patient Registry and all-cause death from the Danish Civil Registration System. In intention-to-treat analyses, cumulative incidences were estimated using the Aalen-Johansen estimator, and hazard ratios (HRs) were calculated using Cox proportional hazards regression. Follow-up began at treatment initiation (June 1, 2014–December 31, 2022) and continued until the first occurrence of an outcome, emigration, or study end (December 31, 2022). Baseline covariates (n=66) were balanced using inverse probability of treatment weighting. Analyses were performed after restriction to patients with HFrEF and stratified by the presence of type 2 diabetes. Results The primary outcome occurred in 703 of 2,860 patients (24.6%) in the empagliflozin group and 1,697 of 6,264 patients (27.1%) in the dapagliflozin group over a median follow-up of 2.0 years. The empagliflozin group had an observed lower risk of the primary outcome compared with the dapagliflozin group (HR=0.85, 95% CI: 0.76–0.93, p0.001) (Figure 2). The HRs for the components of the primary outcome were 0.85 (95% CI: 0.76–0.93) for heart failure rehospitalization and 0.90 (95% CI: 0.75–1.06) for all-cause death. The observed lower risk of the primary outcome in the empagliflozin group compared with the dapagliflozin group appeared consistent in patients with HFrEF (HR=0.85, 95% CI: 0.76–0.94), and in patients with type 2 diabetes (HR=0.85, 95% CI: 0.73–0.97) and without type 2 diabetes (HR=0.89, 95% CI: 0.75–1.03). Conclusions In patients with heart failure, initiation of empagliflozin was associated with a lower risk of heart failure rehospitalization or all-cause death compared with initiation of dapagliflozin, after restriction to patients with HFrEF and regardless of the presence of type 2 diabetes.Figure 1 Figure 2