Semaglutide and Exercise Function in Obesity-Related HFpEF Insights From the STEP-HFpEF Program
BACKGROUND Exercise function quantified by 6-minute walk distance (6MWD) is severely impaired in patients with heart failure with preserved ejection fraction (HFpEF). OBJECTIVES This prespecified secondary analysis of pooled data from the STEP-HFpEF Program (Research Study to Investigate How Well Se...
| Autores: | , , , , , , , , , , , , , |
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| Tipo de recurso: | artículo |
| Estado: | Versión publicada |
| Fecha de publicación: | 2025 |
| País: | España |
| Institución: | INCLIVA |
| Repositorio: | r-INCLIVA. Repositorio Institucional de Producción Científica de INCLIVA |
| OAI Identifier: | oai:incliva.fundanetsuite.com:p20422 |
| Acceso en línea: | https://incliva.portalinvestigacion.com/publicaciones/20422 |
| Access Level: | acceso abierto |
| Palabra clave: | 6-minute walk distance heart failure with preserved ejection fraction obesity semaglutide |
| Sumario: | BACKGROUND Exercise function quantified by 6-minute walk distance (6MWD) is severely impaired in patients with heart failure with preserved ejection fraction (HFpEF). OBJECTIVES This prespecified secondary analysis of pooled data from the STEP-HFpEF Program (Research Study to Investigate How Well Semaglutide Works in People Living With Heart Failure and Obesity) examined factors associated with impaired exercise function at baseline, detailed effects of semaglutide on 6MWD, and on other key trial endpoints according to baseline 6MWD in patients with HFpEF. METHODS Associates of 6MWD were assessed at baseline, and effects of semaglutide on 6MWD were evaluated at early (20 weeks) and final (52 weeks) time points, across subgroups, and according to the magnitude of weight loss achieved. Effects of semaglutide on the dual primary (changes in Kansas City Cardiomyopathy Questionnaire-Clinical Summary Score [KCCQ-CSS] and body weight) and secondary/exploratory endpoints were contrasted by tertiles of baseline 6MWD. RESULTS The authors randomized 1,145 patients to semaglutide or placebo. Compared with patients who had obesity-related HFpEF and higher 6MWD, those with lower 6MWD were older and had lower KCCQ-CSS, higher body mass index and waist circumference, greater systemic inflammation (higher C-reactive protein), and more severe congestion (higher N-terminal pro-B-type natriuretic peptide, more diuretic use). Treatment with semaglutide increased 6MWD compared with placebo, an effect apparent at 20 weeks (treatment difference 14.6 m [95% CI: 8.6-20.7 m; P < 0.0001]) that was maintained at 52 weeks (treatment difference 17.1 m [95% CI: 9.2-25.0 m; P < 0.0001]). Increases in 6MWD with semaglutide (vs placebo) were similar across all relevant subgroups, with no significant interactions. Treatment with semaglutide increased KCCQ-CSS and reduced body weight, reduced C-reactive protein, improved the hierarchical composite (death, heart failure events, change in KCCQ-CSS and 6MWD), and reduced N-terminal pro-B-type natriuretic peptide across the spectrum of baseline 6MWD (all Pinteraction= NS). Each 1-unit decrease in body mass index on treatment with semaglutide was associated with a 4.1 m (95% CI: 2.4-5.7 m) increase in 6MWD (P < 0.0001). CONCLUSIONS In patients with obesity-related HFpEF, impaired 6MWD is most strongly associated with excess adiposity, congestion, and inflammation. Semaglutide-mediated improvements in HF-related symptoms, physical limitations, and exercise function were consistent across the spectrum of baseline 6MWD, observed as early as 20 weeks after the initiation of treatment, preceding maximal weight loss. The effects were consistent across subgroups. There was strong correlation between greater magnitude of weight loss and greater improvements in 6MWD. (Research Study to Investigate How Well Semaglutide Works in People Living With Heart Failure and Obesity [STEP-HFpEF], NCT04788511; Research Study to Look at How Well Semaglutide Works in People Living With Heart Failure, Obesity and Type 2 Diabetes [STEP-HFpEF DM], NCT04916470) (JACC Heart Fail. 2025;13:102660) (c) 2025 by the American College of Cardiology Foundation. |
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