Journal Article

Dapagliflozin in Heart Failure with Mildly Reduced or Preserved Ejection Fraction

Petersson, Magnus, Kitakaze, Masafumi, Lindholm, Daniel, O’Meara, Eileen, de Boer, Rudolf A., Drozdz, Jaroslaw, Thierer, Jorge, Solomon, Scott D., Hernandez, Adrian F., Janssens, Stefan P., Kosiborod, Mikhail N., Bachus, Erasmus, Inzucchi, Silvio E., Vaduganathan, Muthiah, Tereshchenko, Sergey N., Martinez, Felipe, Pham, Vinh Nguyen, Cabrera Honorio, Jose Walter, Langkilde, Anna Maria, DeMets, David, Merkely, Béla, Wilderäng, Ulrica, Shah, Sanjiv J., Al Habeeb, Waleed, Fang, James C., Katova, Tzvetana, Dobreanu, Dan, Zaozerska, Natalia, Lam, Carolyn S.P., McMurray, John J.V., Claggett, Brian, Saraiva, Jose Francisco Kerr, Alcocer-Gamba, Marco Antonio, Han, Yaling, Desai, Akshay S., Chiang, Chern-En, Comin-Colet, Josep, Belohlavek, Jan, Borleffs, C. Jan Willem, Vardeny, Orly, Jhund, Pardeep S., Verma, Subodh

2022

Overview

Sodium-glucose cotransporter 2 (SGLT2) inhibitors reduce the risk of hospitalization for heart failure and cardiovascular death among patients with chronic heart failure and a left ventricular ejection fraction of 40% or less. Whether SGLT2 inhibitors are effective in patients with a higher left ventricular ejection fraction remains less certain. We randomly assigned 6263 patients with heart failure and a left ventricular ejection fraction of more than 40% to receive dapagliflozin (at a dose of 10 mg once daily) or matching placebo, in addition to usual therapy. The primary outcome was a composite of worsening heart failure (which was defined as either an unplanned hospitalization for heart failure or an urgent visit for heart failure) or cardiovascular death, as assessed in a time-to-event analysis. Over a median of 2.3 years, the primary outcome occurred in 512 of 3131 patients (16.4%) in the dapagliflozin group and in 610 of 3132 patients (19.5%) in the placebo group (hazard ratio, 0.82; 95% confidence interval [CI], 0.73 to 0.92; P<0.001). Worsening heart failure occurred in 368 patients (11.8%) in the dapagliflozin group and in 455 patients (14.5%) in the placebo group (hazard ratio, 0.79; 95% CI, 0.69 to 0.91); cardiovascular death occurred in 231 patients (7.4%) and 261 patients (8.3%), respectively (hazard ratio, 0.88; 95% CI, 0.74 to 1.05). Total events and symptom burden were lower in the dapagliflozin group than in the placebo group. Results were similar among patients with a left ventricular ejection fraction of 60% or more and those with a left ventricular ejection fraction of less than 60%, and results were similar in prespecified subgroups, including patients with or without diabetes. The incidence of adverse events was similar in the two groups. Dapagliflozin reduced the combined risk of worsening heart failure or cardiovascular death among patients with heart failure and a mildly reduced or preserved ejection fraction. (Funded by AstraZeneca; DELIVER ClinicalTrials.gov number, NCT03619213.).

• Publisher: Massachusetts Medical Society
• Subject: Antidiabetics / Benzhydryl Compounds - adverse effects / Benzhydryl Compounds - therapeutic use / Cardiology / Cardiology General / Congestive heart failure / Coronaviruses / COVID-19 / Death / Diabetes / Diabetes mellitus / Diabetes Mellitus, Type 2 - complications / Diabetes Mellitus, Type 2 - drug therapy / Disease prevention / Ejection fraction / Glucosides - adverse effects / Glucosides - therapeutic use / Heart Failure / Heart Failure - complications / Heart Failure - drug therapy / Heart Failure - mortality / Heart Failure - physiopathology / Hospitalization / Humans / Inhibitor drugs / Placebos / Sodium-glucose cotransporter / Sodium-Glucose Transporter 2 Inhibitors - adverse effects / Sodium-Glucose Transporter 2 Inhibitors - pharmacology / Sodium-Glucose Transporter 2 Inhibitors - therapeutic use / Stroke Volume - drug effects / Ventricle / Ventricular Function, Left - drug effects