Cardiovascular and Kidney Outcomes with Empagliflozin in Heart Failure

Background Sodium-glucose cotransporter 2 inhibitors reduce the risk of hospitalizations for heart failure in patients with or without diabetes. More evidence is needed regarding their effects across the broad spectrum of heart failure, including those with a markedly reduced ejection fraction.

Methods In the double-blind EMPEROR-Reduced trial, we randomly assigned 3730 patients with class II-IV heart failure and an ejection fraction ≤40% to receive empagliflozin (10 mg once daily) or placebo, in addition to recommended therapy. The primary outcome was a composite of cardiovascular death and hospitalization for worsening heart failure.

Results Over a median of 16 months, the primary outcome occurred in 361 of 1863 patients (19.4%) in the empagliflozin group and in 462 of 1867 patients (24.7%) in the placebo group (hazard ratio 0.75; 95% CI: 0.65–0.86; P < 0.001). The effect of empagliflozin on the primary outcome was consistent in patients regardless the presence or absence of diabetes. 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: 0.58–0.85; P < 0.001). The rate of decline in estimated glomerular filtration rate was slower in the empagliflozin group than in the placebo group (–0.55 vs –2.28 ml/min/1.73m2/year), P < 0.001, and empagliflozin-treated patients had a lower risk of serious kidney outcomes. Uncomplicated genital tract infections were reported more frequently with empagliflozin.

Conclusions Empagliflozin reduced the combined risk of cardiovascular death or hospitalization for heart failure, regardless of the presence or absence of diabetes.

Interessenskonflikt

FZ has recently received steering committee or advisory board fees from Amgen, AZ, Bayer, BI, Boston Scientific, Cardior, CVRx, Janssen, Livanova, Merck, Mundipharma, Novartis, Novo Nordisk (NN), and Vifor Fresenius.

JB reports consulting fees from BI, Cardior, CVRx, Foundry, G3 Pharma, Imbria, Impulse Dynamics, Innolife, Janssen, LivaNova, Luitpold, Medtronic, Merck, Novartis, NN, Relypsa, Roche, Sanofi, Sequana Medical, V-Wave Ltd., and Vifor.

GF reports lectures and/or committee member contributions in trials sponsored by Medtronic, Vifor, Servier, Novartis, Bayer, Amgen and BI.

SJP is a consultant for BI.

WJ, JS, CZ, and MB are employees of BI.

SDA reports grants and personal fees from Vifor Int., Abbott Vascular, AZ, Bayer, Brahms, BI, Cardiac Dimensions, Novartis, Occlutech, Servier, and Vifor Int.

MP reports personal fees from AbbVie, Akcea, Amarin, AZ, Amgen, BI.

Publication History

Article published online:
06 May 2021