EMPEROR-Reduced trial: Empagliflozin in patients with heart failure and low ejection fraction

Abstract

Background: In patients with heart failure with and without diabetes, inhibitors of sodium-glucose cotransporter 2 (SGLT2) reduce the risk of serious heart failure events. More evidence is needed regarding the effects of SGLT2 inhibitors in patients across the broad spectrum of heart failure, including those with markedly reduced ejection fraction and higher natriuretic peptide levels. Methods: In this phase III, placebo-controlled trial, we randomly assigned 3,730 patients with New York Heart Association class II, III, or IV heart fail-ure and an ejection fraction of 40 % or less to receive either empagliflozin (10 mg once daily) or placebo, in addition to recommended therapy. The primary outcome was a composite of death from cardiovascular causes and hospitalization for worsening heart failure. A secondary endpoint was effect on renal functions. Results: Over a median of 16 months, the primary outcome occurred in 361 of 1,863 patients (19.4 %) in the empagliflozin group and in 462 of 1,867 patients (24.7 %) in the placebo group (hazard ratio, 0.75; 95 % confidence interval [CI], 0.65 to 0.86; P < 0.001). The effect of empagliflozin on the primary outcome was consistent in patients with and without diabetes and in those taking and not taking sacubitril/valsartan. The total number of hospitalizations for heart failure was lower in the empagliflozin group than in the placebo group (hazard ratio, 0.70; 95 % CI, 0.58 to 0.85; P < 0.001). The rate of decline in eGFR was slower in the empagliflozin group than in the placebo group. The frequency of adverse events related to hypotension, renal dysfunction, and hypoglycemia did not differ between the treatment groups. Conclusions: Across a broad spectrum of patients with heart failure and a reduced ejection fraction, empagliflozin reduced the risk of death from cardiovascular causes or hospitalization for heart failure, regardless of the presence or absence of diabetes and background therapy for heart failure.