Early treatment with a sodium-glucose co-transporter 2 inhibitor in high-risk patients with acute heart failure: Rationale for and design of the EMPA-AHF trial

Abstract

The aim of the EMPA-AHF trial is to clarify whether early initiation of a sodium-glucose co-transporter 2 inhibitor before clinical stabilization is safe and beneficial for patients with acute heart failure (AHF) who are at a high risk of adverse events. The EMPA-AHF trial is a randomized, double-blind, placebo-controlled, multicentre trial examining the efficacy and safety of early initiation of empagliflozin (10 mg once daily). In total, 500 patients admitted for AHF will be randomized 1:1 to either empagliflozin 10 mg daily or placebo at 47 sites in Japan. Study entry requires hospitalization for AHF with dyspnoea, signs of volume overload, elevated natriuretic peptide, and at least one of the following criteria: estimated glomerular filtration rate <60 mL/min/1.73 m2; already taking ≥40 mg of furosemide daily before hospitalization; and urine output of <300 mL within 2 hours after an adequate dose of intravenous furosemide. Patients will be randomized within 12 hours of hospital presentation, with treatment continued up to 90 days. The primary outcome is the clinical benefit of empagliflozin on the win ratio for a hierarchical composite endpoint consisting of death within 90 days, heart failure rehospitalization within 90 days, worsening heart failure during hospitalization, and urine output within 48 hours after treatment initiation. The EMPA-AHF trial is the first to evaluate the efficacy and safety of early initiation of empagliflozin in patients with AHF considered to be at high risk under conventional treatment.