The sodium-glucose cotransporter 2 inhibitor empagliflozin reduces the risk of cardiovascular death or heart failure hospitalization in patients with chronic heart failure, but whether empagliflozin also improves clinical outcomes when initiated in patients who are hospitalized for acute heart failure is unknown. In this double-blind trial (EMPULSE; NCT04157751 ), 530 patients with a primary diagnosis of acute de novo or decompensated chronic heart failure regardless of left ventricular ejection fraction were randomly assigned to receive empagliflozin 10 mg once daily or placebo. Patients were randomized in-hospital when clinically stable (median time from hospital admission to randomization, 3 days) and were treated for up to 90 days. The primary outcome of the trial was clinical benefit, defined as a hierarchical composite of death from any cause, number of heart failure events and time to first heart failure event, or a 5 point or greater difference in change from baseline in the Kansas City Cardiomyopathy Questionnaire Total Symptom Score at 90 days, as assessed using a win ratio. More patients treated with empagliflozin had clinical benefit compared with placebo (stratified win ratio, 1.36; 95% confidence interval, 1.09-1.68; P = 0.0054), meeting the primary endpoint. Clinical benefit was observed for both acute de novo and decompensated chronic heart failure and was observed regardless of ejection fraction or the presence or absence of diabetes. Empagliflozin was well tolerated; serious adverse events were reported in 32.3% and 43.6% of the empagliflozin- and placebo-treated patients, respectively. These findings indicate that initiation of empagliflozin in patients hospitalized for acute heart failure is well tolerated and results in significant clinical benefit in the 90 days after starting treatment.

1st Department of Medicine Faculty of Medicine Mannheim University of Heidelberg Mannheim Germany

1st Department of Medicine Masaryk University Hospital Brno Czech Republic

Boehringer Ingelheim International GmbH Ingelheim Germany

Boehringer Ingelheim Pharmaceuticals Inc Ridgefield CT USA

Cardiovascular Research and Development Center Department of Surgery and Physiology Faculty of Medicine of the University of Porto Porto Portugal

Comprehensive Heart Failure Centre University and University Hospital of Würzburg Würzburg Germany

Department of Cardiology Beijing Anzhen Hospital Capital Medical University Beijing China

Department of Cardiology Division of Medicine Akershus University Hospital Lørenskog Norway

Department of Cardiology Gentofte University Hospital Copenhagen Copenhagen Denmark

Department of Cardiology IRCCS San Raffaele Pisana Rome Italy

Department of Cardiology Military Hospital Budapest Hungary

Department of Cardiovascular Medicine Osaka University Graduate School of Medicine Osaka Japan

Department of Cardiovascular Sciences Clinical Cardiology Belgium University Hospital Katholieke Universiteit Leuven Leuven Belgium

Department of Electrocardiology Medical University of Lodz Central Clinical Hospital Lodz Poland

Department of Emergency Medicine Vanderbilt University Medical Center and Geriatric Research and Education Clinical Care Tennessee Valley Healthcare Facility VA Medical Center Nashville TN USA

Division of Cardiology Duke University Medical Center Durham NC USA

Duke Clinical Research Institute Duke University Medical Center Durham NC USA

Elderbrook Solutions GmbH on behalf of Boehringer Ingelheim Pharma GmbH and Co KG Biberach Germany

Faculty of Medicine Rutgers University New Brunswick NJ USA

George Institute for Global Health Sydney New South Wales Australia

Haga Teaching Hospital Den Haag The Netherlands

Hospital Universitari de Bellvitge Barcelona Spain

Inova Heart and Vascular Institute Falls Church VA USA

Institute of Heart Diseases Medical University Wroclaw Poland

Klinikum Ludwigshafen Ludwigshafen Germany

Saint Luke's Mid America Heart Institute Kansas City MO USA

Saw Swee Hock School of Public Health National University of Singapore and the National University Health System Singapore Singapore

School of Medicine University of Missouri Kansas City Kansas City MO USA

Section of Cardiology Max Rady College of Medicine University of Manitoba Winnipeg Manitoba Canada

Section of Cardiology Sahlgrenska University Hospital University of Gothenburg Gothenburg Sweden

Section of Cardiology San Francisco Veterans Affairs Medical Center and School of Medicine University of California San Francisco San Francisco CA USA

Université de Lorraine Inserm INI CRCT Centre Hospitalier Régional Universitaire Nancy France

University Hospital Jena Jena Germany

University of Groningen Department of Cardiology University Medical Center Groningen Groningen The Netherlands

University of New South Wales Sydney New South Wales Australia

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ClinicalTrials.gov
NCT04157751