J Am Coll Cardiol

ADA 2024: Semaglutide improves symptoms in men, women with HFpEF

June 26, 2024

In patients with obesity-related heart failure with preserved ejection fraction (HFpEF), women have greater symptom severity, greater exercise limitation, and more severe systemic inflammation than men. Findings from STEP-HFpEF trial (Research Study to Investigate How Well Semaglutide Works in People Living With Heart Failure and Obesity) demonstrate that treatment with semaglutide reduced body weight in both women and men but resulted in greater weight loss in women. Despite greater reductions in weight in women than men, semaglutide produced similar, clinically meaningful improvements in HF-related symptoms, physical limitations, and exercise function, along with reductions in inflammation and natriuretic peptides, regardless of sex. The findings were presented at the recent American Diabetes Association annual meeting.

• Using pooled data from the STEP-HFpEF and STEP-HFpEF DM trials, patients with HF, LVEF ≥45%, BMI ≥30 kg/m^2, and Kansas City Cardiomyopathy Questionnaire Clinical Summary Score (KCCQ-CSS) <90 points were randomized 1:1 to once-weekly semaglutide 2.4 mg or matched placebo for 52 weeks. Primary endpoints were KCCQ-CSS change and percentage change in body weight; confirmatory secondary endpoints (6-minute walking distance [6MWD] change; hierarchical composite endpoint comprising all-cause death, HF events, changes in KCCQ-CSS, and 6MWD; and C-reactive protein) were also compared between sexes.
• Of 1,145 patients, 49.7% were women. Women had higher BMI, LVEF, C-reactive protein, and worse HF symptoms, and were less likely to have atrial fibrillation or coronary artery disease vs. men.
• Semaglutide improved KCCQ-CSS regardless of sex with a mean difference in women of +7.6 points and men +7.5 points, but reduced body weight more in women with a mean difference of -9.6% vs. -7.2%.
• Semaglutide improved 6MWD (P interaction = 0.21) and the hierarchical composite endpoint (P interaction = 0.66) in both sexes.

Sources:

Verma S, et al; STEP-HFpEF Trial Committees and Investigators. (2024, June 19). J Am Coll Cardiol. Efficacy of Semaglutide by Sex in Obesity-Related Heart Failure With Preserved Ejection Fraction: STEP-HFpEF Trials. https://pubmed.ncbi.nlm.nih.gov/38913003/

(2024, June 24). ADA Meeting News. STEP trials show heart failure benefit with or without diabetes, could transform HFpEF treatment. https://www.adameetingnews.org/step-trials-show-heart-failure-benefit-with-or-without-diabetes-could-transform-hfpef-treatment/