Empagliflozin in De Novo Vs Acute Decompensated Chronic Heart Failure: A Prespecified Analysis from EMPULSE

BACKGROUND:In EMPULSE (A Study to Test the Effect of Empagliflozin in Patients Who Are in Hospital for Acute Heart Failure), the sodium-glucose cotransporter 2 inhibitor empagliflozin improved clinical outcomes in patients hospitalized for heart failure (HF). OBJECTIVES:This prespecified analysis examined efficacy, safety, and tolerability of empagliflozin in subgroups with de novo heart failure (NHF) vs acute decompensated heart failure (ADHF). METHODS:After stabilization, participants were randomized 1:1 to empagliflozin 10 mg/d or placebo, stratified by HF status (NHF: n = 175; ADHF: n = 355). The primary endpoint was a hierarchical composite of death, worsening HF, or ≥5-point difference in Kansas City Cardiomyopathy Questionnaire-Total Symptom Score (KCCQ-TSS) change at day 90, assessed using a win ratio. RESULTS:Participants with NHF were younger, had fewer comorbidities, had higher blood pressure and heart rate, and better KCCQ-TSS. Prescription of diuretic agents was similar between subgroups. The win ratio was 1.29 (95% CI: 0.89-1.89) for NHF and 1.39 (95% CI: 1.07-1.81) for ADHF (Pinteraction = 0.759). There were no interactions between NHF and ADHF for the primary endpoint, its components, or secondary endpoints, except diuretic response, which was greater with empagliflozin in NHF than in ADHF from day 15 (mean difference vs placebo: -5.11 [Q1-Q3: -7.89 to -2.32] vs -0.97 [Q1-Q3: -2.91 to 0.96] kg per mean daily loop diuretic dose, Pinteraction = 0.017), with even greater between-group differences at days 30 and 90. Frequencies of adverse events were consistently lower with empagliflozin vs placebo. CONCLUSIONS:In-hospital initiation of empagliflozin produced similar clinical benefits in NHF and ADHF despite the reduced diuretic response in participants with ADHF and was well tolerated. This supports in-hospital initiation of empagliflozin in all patients with acute HF (A Study to Test the Effect of Empagliflozin in Patients Who Are in Hospital for Acute Heart Failure [EMPULSE]; NCT04157751).