Mineralocorticoid receptor antagonist use and the effects of empagliflozin on clinical outcomes in patients admitted for acute heart failure: findings from EMPULSE.

Abstract

In patients hospitalized for acute heart failure (AHF) empagliflozin produced greater clinical benefit than placebo. Many patients with AHF are treated with mineralocorticoid receptor antagonists (MRAs). The interplay between empagliflozin and MRAs in AHF is yet to be explored. To study the efficacy and safety of empagliflozin versus placebo according to MRA use at baseline in the EMPULSE trial (NCT04157751). In this analysis all comparisons were performed between empagliflozin and placebo, stratified by baseline MRA use. The primary outcome included all-cause death, HF events, and a ≥5 point difference in KCCQ-TSS at 90 days, assessed using the win ratio (WR). First HF hospitalization or cardiovascular death was a secondary outcome. From the 530 patients randomized, 276 (52%) were receiving MRA at baseline. MRA users were younger, had lower ejection fraction, better renal function, and higher KCCQ scores. The primary outcome showed benefit of empagliflozin irrespective of baseline MRA use (WR=1.46, 95%CI=1.08-1.97 and WR=1.27, 95%CI=0.93-1.73 in MRA users and non-users, respectively; interactionP=0.52). The effect of empagliflozin on first HF hospitalization or cardiovascular death was not modified by MRA use (HR=0.58, 95%CI=0.30-1.11 and HR=0.85, 95%CI=0.47-1.52 in MRA users and non-users, respectively; interactionP=0.39). Investigator-reported and severe hyperkalemia events were infrequent (<6%) irrespective of MRA use. In patients admitted for AHF, initiation of empagliflozin produced clinical benefit and was well tolerated irrespective of background MRA use. These findings support the early use of empagliflozin on top of MRA therapy in patients admitted for AHF. This article is protected by copyright. All rights reserved.