Empagliflozin vs Dapagliflozin in Heart Failure: a Target Trial Emulation

No randomized trial has compared, head-to-head, the effects of empagliflozin and dapagliflozin in patients with heart failure.

This nationwide, prospective, new-user, active-comparator cohort study emulated a pragmatic target trial comparing heart failure rehospitalization and all-cause death risks in adults with heart failure who were initiating empagliflozin vs dapagliflozin. To study the effects of initiating and sustaining treatment analyses, we calculated 1- and 5-year risks and risk ratios (RRs) of outcomes. Follow-up began at treatment initiation (June 1, 2014-December 31, 2022) and continued until the first of an outcome, emigration, December 31, 2022, or 5 years of follow-up. Inverse probability of treatment and censoring weights were applied to balance baseline covariates and, in analyses of sustained treatment, to account for nonadherence.

Of our patients, 2860 initiated empagliflozin, and 6264 initiated dapagliflozin (median age, 70 [IQR, 61-78] years; 25% females). In the effect-of-initiating-treatment analyses, heart failure rehospitalization risks at 1 year were 16.1% in the empagliflozin group vs 19.8% in the dapagliflozin group (RR, 0.81 [95% CI 0.71-0.94]) and 30.5% vs 33.4% at 5 years (RR, 0.92 [95% CI 0.79-1.06]). The risks of all-cause death were 6.7% vs 6.9% at 1 year (RR, 0.97 [95% CI 0.74-1.27]) and 23.4% vs 23.8% at 5 years (RR, 0.98 [95% CI 0.77-1.25]). In the effect of sustained treatment analyses, the RRs for heart failure rehospitalization, comparing the empagliflozin with the dapagliflozin group, were 0.81 (95% CI 0.70-0.94) at 1 year and 0.82 (95% CI 0.67-1.00) at 5 years. The corresponding RRs for all-cause death were 1.12 (95% CI 0.84-1.49) at 1 year and 1.00 (95% CI 0.70-1.44) at 5 years.

Although this study cannot exclude lower short- and long-term risks of rehospitalization due to HF among patients with heart failure who initiate empagliflozin compared with dapagliflozin, no substantial difference was observed in the risks of all-cause death.