Clinical question: Does treatment with semaglutide lead to a reduction in symptoms and physical limitations and improve exercise function in patients with heart failure with preserved ejection fraction (HFpEF) and obesity? Does it affect hospitalizations?
Background: Patients with HFpEF and obesity have more adverse clinical features and hemodynamics, more symptoms, worse functional capacity, and more severely impaired quality of life. There is growing evidence that obesity and excess adiposity may play a role in the development and progression of HFpEF.
Study design: Randomized, double-blinded, placebo-controlled trial
Setting: 13 countries, 96 sites (Asia, Europe, North and South America)
Synopsis: 529 patients with HFpEF and obesity with BMI over 30 were randomly assigned to receive a once-weekly dose of 2.4 mg semaglutide (263) or placebo (266) for 1 year. The trial had two primary endpoints looking at changes in the Kansas City Cardiomyopathy Questionnaire clinical summary score (KCCQ-CSS, range 0 to 100, higher score meaning fewer symptoms) and change in weight. Secondary endpoints included exercise function measured by 6-minute walk distance, HF events, and a composite endpoint which included death. Patients in the semaglutide arm had a change of 16.6 points in KCCQ-CSS from baseline compared to 8.7 in the placebo arm (estimated difference of 7.8 points; 95% confidence interval [CI], 4.8 to 10.9; P <0.001). In the semaglutide arm, the mean percentage change in body weight was -13.3% compared to -2.6% in placebo (estimated difference -10.7; 95% CI, -11.9 to -9.4, P <0.001). Patients who received semaglutide had a change of 21.5 m in the 6-minute walk test compared with 1.2 m in placebo (estimated difference, 20.3 m; CI, 8.6 to 32.1; P <0.001). Limitations include few nonwhite participants, not being powered to detect clinical events like urgent visits and hospitalization for heart failure, and follow-up continuing for only one year.
Bottom line: Patients with HFpEF and obesity who were treated with semaglutide had a larger reduction in symptoms and physical limitations and had improved exercise function and weight loss compared to placebo.
Citation: Borlaug BA, et al. Semaglutide in HFpEF across obesity class and by body weight reduction: a prespecified analysis of the STEP-HFpEF trial. Nat Med. 2023;29(9):2358-65.
Dr. Barot is the medical director of the virtual hospital at Atrium Health Wake Forest Baptist, and an assistant professor of hospital medicine at Wake Forest School of Medicine, both in Winston-Salem, N.C.