In the EMPEROR-Reduced Trial, empagliflozin was demonstrated to reduce cardiorenal outcomes and improve quality of life in patients with HFrEF. We examined whether the benefit of empagliflozin was consistent across the doses and combinations of baseline heart failure therapies.

The primary outcome of time to cardiovascular (CV) death or hospitalization for heart failure (HHF) was examined in patients receiving ACEi or ARB (RAASi), MRA or beta-blockers (BB) at ≥50% or <50% of target dose. Furthermore, the primary outcome was examined in patients receiving baseline combination therapy: RAASi+BB; RAASi+BB+MRA; and ARNI+BB+MRA.

At baseline, of the 3730 patients randomized, 26.8%, 61.5%, and 48.9% were treated with ≥50% of target doses of RAASi, MRA or BB respectively. Additionally, 66.7%, 17.5%, 48.4%, 13.8%, 84.1%, 61.1%, and 13.4% were treated with combination of either RAASi+BB, RAASi+BB (≥50%), RAASi+BB+MRA, RAASi+BB (≥50%)+MRA, RAASi or ARNI+BB, RAASi or ARNI+BB+MRA or ARNI+BB+MRA. Across all sub-groups, the hazard ratio for the primary outcome was consistent with the overall estimate of 0.75 (0.65 to 0.86; P<0.001) in empagliflozin vs. placebo treated patients with no heterogeneity by subgroup interaction (Figure 1). KCCQ-CSS improved across all subgroups. Tolerability was similar between groups.

Empagliflozin's beneficial effects in HFrEF are observed consistently regardless of the doses and combinations of other foundational drugs for heart failure.