Abstract
Background: More women than men have heart failure with preserved ejection fraction (HFpEF). Objectives: The purpose of this study was to assess baseline characteristics and treatment effect of semaglutide by sex across the STEP-HFpEF (Research Study to Investigate How Well Semaglutide Works in People Living With Heart Failure and Obesity) program. Methods: In a prespecified secondary analysis of pooled data from STEP-HFpEF and STEP-HFpEF DM (Research Study to Look at How Well Semaglutide Works in People Living With Heart Failure, Obesity and Type 2 Diabetes), patients with heart failure (HF), left ventricular ejection fraction ≥45%, body mass index ≥30 kg/m2, 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. Dual primary endpoints (KCCQ-CSS change and percentage change in body weight) and 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 compared between sexes. Results: Of 1,145 patients, 570 (49.7%) were women. Women had higher body mass index, left ventricular ejection fraction, 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 (mean difference in women +7.6 points [95% CI: 4.5-10.7 points]; men +7.5 points [95% CI: 4.3-10.6 points]; P interaction = 0.94) but reduced body weight more in women (mean difference in women −9.6% [95% CI: −10.9% to −8.4%]; men −7.2% [95% CI: −8.4% to −6.0%]; P interaction = 0.006). Semaglutide improved 6MWD (P interaction = 0.21) and the hierarchical composite endpoint (P interaction = 0.66) in both sexes. Fewer serious adverse events were reported with semaglutide vs placebo. Conclusions: In patients with obesity-related HFpEF, semaglutide 2.4 mg reduced body weight to a greater extent in women, and produced similar improvements in HF-related symptoms, physical limitations, and exercise function, regardless of sex.
| Original language | English (US) |
|---|---|
| Pages (from-to) | 773-785 |
| Number of pages | 13 |
| Journal | Journal of the American College of Cardiology |
| Volume | 84 |
| Issue number | 9 |
| DOIs | |
| State | Published - Aug 27 2024 |
Funding
The authors are indebted to the trial participants, the investigators, and the trial site staff. Administrative support was provided by Judah Lynch, MRes, of OPEN Health Communications, funded by Novo Nordisk A/S. The authors are indebted to the trial participants, the investigators, and the trial site staff. Administrative support was provided by Judah Lynch, MRes, of Apollo, OPEN Health Communications, funded by Novo Nordisk A/S. Academic members (Drs Kosiborod, Borlaug, Butler, Davies, Kitzman, Petrie, Shah, and Verma) of the Steering Committee and Novo Nordisk conceived and designed the study. The first draft of the manuscript was prepared by Dr Subodh Verma. All authors interpreted the data, contributed writing, approved the final version, vouched for data accuracy and fidelity to the protocol, and decided to submit. Data will be shared with bona fide researchers submitting a research proposal approved by the independent review board. Access request proposals can be found on the Novo Nordisk trials website. Data will be made available after research completion and approval of the product and product use in the European Union and the United States. Individual participant data will be shared in data sets in a deidentified/anonymized format.
Keywords
- heart failure
- obesity
- semaglutide
- sex
ASJC Scopus subject areas
- Cardiology and Cardiovascular Medicine
