Tirzepatide for Heart Failure with Preserved Ejection Fraction and Obesity

作者：Milton Packer, Michael R. Zile, Christopher M. Kramer, Seth J. Baum, Sheldon E. Litwin, Venu Menon, Junbo Ge, Govinda Weerakkody, Ou Yang, Mathijs C. Bunck, Karla Hurt, Masahiro Murakami, Barry A. Borlaug · 发表于：New England Journal of Medicine · 年份：2024 · DOI：10.1056/nejmoa2410027 · 被引用次数：936 · 研究领域：Diabetes Treatment and Management、Cardiovascular Function and Risk Factors、Heart Failure Treatment and Management

BACKGROUND: Obesity increases the risk of heart failure with preserved ejection fraction. Tirzepatide, a long-acting agonist of glucose-dependent insulinotropic polypeptide and glucagon-like peptide-1 receptors, causes considerable weight loss, but data are lacking with respect to its effects on cardiovascular outcomes. METHODS: In this international, double-blind, randomized, placebo-controlled trial, we randomly assigned, in a 1:1 ratio, 731 patients with heart failure, an ejection fraction of at least 50%, and a body-mass index (the weight in kilograms divided by the square of the height in meters) of at least 30 to receive tirzepatide (up to 15 mg subcutaneously once per week) or placebo for at least 52 weeks. The two primary end points were a composite of adjudicated death from cardiovascular causes or a worsening heart-failure event (assessed in a time-to-first-event analysis) and the change from baseline to 52 weeks in the Kansas City Cardiomyopathy Questionnaire clinical summary score (KCCQ-CSS; scores range from 0 to 100, with higher scores indicating better quality of life). RESULTS: A total of 364 patients were assigned to the tirzepatide group and 367 to the placebo group; the median duration of follow-up was 104 weeks. Adjudicated death from cardiovascular causes or a worsening heart-failure event occurred in 36 patients (9.9%) in the tirzepatide group and in 56 patients (15.3%) in the placebo group (hazard ratio, 0.62; 95% confidence interval [CI], 0.41 to 0.95;...