Semaglutide in HFpEF across obesity class and by body weight reduction: a prespecified analysis of the STEP-HFpEF trial


Por: Borlaug B, Kitzman D, Davies M, Rasmussen S, Barros E, Butler J, Einfeldt M, Hovingh G, Moller D, Petrie M, Shah S, Verma S, Abhayaratna W, Ahmed F, Chopra V, Ezekowitz J, Fu M, Ito H, Lelonek M, Melenovsky V, Nunez J, Perna E, Schou M, Senni M, van der Meer P, Von Lewinski D, Wolf D, Kosiborod M

Publicada: 1 sep 2023 Ahead of Print: 1 ago 2023
Resumen:
In the STEP-HFpEF trial, semaglutide improved symptoms, physical limitations and exercise function and reduced body weight in patients with obesity phenotype of heart failure and preserved ejection fraction (HFpEF). This prespecified analysis examined the effects of semaglutide on dual primary endpoints (change in Kansas City Cardiomyopathy Questionnaire-Clinical Summary Score (KCCQ-CSS) and body weight) and confirmatory secondary endpoints (change in 6-minute walk distance (6MWD), hierarchical composite (death, HF events, change in KCCQ-CSS and 6MWD) and change in C-reactive protein (CRP)) across obesity classes I-III (body mass index (BMI) 30.0-34.9 kg m-2, 35.0-39.9 kg m-2 and & GE;40 kg m-2) and according to body weight reduction with semaglutide after 52 weeks. Semaglutide consistently improved all outcomes across obesity categories (P value for treatment effects x BMI interactions = not significant for all). In semaglutide-treated patients, improvements in KCCQ-CSS, 6MWD and CRP were greater with larger body weight reduction (for example, 6.4-point (95% confidence interval (CI): 4.1, 8.8) and 14.4-m (95% CI: 5.5, 23.3) improvements in KCCQ-CSS and 6MWD for each 10% body weight reduction). In participants with obesity phenotype of HFpEF, semaglutide improved symptoms, physical limitations and exercise function and reduced inflammation and body weight across obesity categories. In semaglutide-treated patients, the magnitude of benefit was directly related to the extent of weight loss. Collectively, these data support semaglutide-mediated weight loss as a key treatment strategy in patients with obesity phenotype of HFpEF. ClinicalTrials.gov identifier: NCT04788511. In a prespecified secondary analysis of the STEP-HFpEF trial, semagludtide treatment was associated with improvements in KCCQ-CSS and body weight, as well as trial secondary endpoints, across the spectrum of obesity classes, with the magnitude of beneficial effects being proportional to the extent of weight loss.

Filiaciones:
Borlaug B:
 Mayo Clin, Dept Cardiovasc Med, Rochester, MN USA

Kitzman D:
 Wake Forest Univ, Bowman Gray Sch Med, Dept Cardiovasc Med, Winston Salem, NC USA

 Wake Forest Univ, Bowman Gray Sch Med, Sect Geriatr & Gerontol, Winston Salem, NC USA

Davies M:
 Univ Leicester, Diabet Res Ctr, Leicester, England

 NIHR Leicester Biomed Res Ctr, Leicester, England

Rasmussen S:
 Novo Nord AS, Soborg, Denmark

Barros E:
 Novo Nord AS, Soborg, Denmark

Butler J:
 Baylor Scott & White Res Inst, Dallas, TX USA

 Univ Mississippi, Dept Med, Jackson, MS USA

Einfeldt M:
 Novo Nord AS, Soborg, Denmark

Hovingh G:
 Novo Nord AS, Soborg, Denmark

Moller D:
 Novo Nord AS, Soborg, Denmark

Petrie M:
 Univ Glasgow, Sch Cardiovasc & Metab Hlth, Glasgow, Scotland

Shah S:
 Northwestern Univ, Dept Med, Div Cardiol, Feinberg Sch Med, Chicago, IL USA

Verma S:
 Univ Toronto, Michaels Hosp, Li Ka Shing Knowledge Inst St, Div Cardiac Surg,Unity Hlth Toronto, Toronto, ON, Canada

Abhayaratna W:
 Australian Natl Univ, Coll Hlth & Med, Canberra, ACT, Australia

Ahmed F:
 Univ Manchester, Fac Biol Med & Hlth, Div Cardiovasc Sci, Manchester, England

Chopra V:
 Max Super Specialty Hosp, Clin Cardiol Heart Failure & Res, New Delhi, India

Ezekowitz J:
 Univ Alberta, Edmonton, AB, Canada

Fu M:
 Sahlgrens Univ Hosp, Dept Med, Sect Cardiol, Gothenburg, Sweden

Ito H:
 Kawasaki Med Sch, Dept Gen Internal Med 3, Okayama, Japan

Lelonek M:
 Med Univ Lodz, Dept Noninvas Cardiol, Lodz, Poland

Melenovsky V:
 Inst Clin & Expt Med IKEM, Prague, Czech Republic

Nunez J:
 Univ Valencia, Hosp Clin Univ Valencia, INCLIVA, Valencia, Spain

 CIBER Cardiovasc, Valencia, Spain

Perna E:
 Inst Cardiol JF Cabral, Corrientes, Argentina

Schou M:
 Univ Copenhagen, Herlev Gentofte Hosp, Dept Cardiol, Herlev, Denmark

Senni M:
 ASST Papa Giovanni XXIII Hosp, Cardiovasc Dept, Bergamo, Italy

van der Meer P:
 Univ Groningen, Univ Med Ctr Groningen, Dept Cardiol, Groningen, Netherlands

Von Lewinski D:
 Med Univ Graz, Div Cardiol, Graz, Austria

Wolf D:
 Univ Freiburg, Fac Med, Med Ctr, Cardiol & Angiol, Freiburg, Germany

Kosiborod M:
 Univ Missouri, St Lukes Mid Amer Heart Inst, Sch Med, Dept Cardiovasc Dis, Kansas City, MO 65211 USA
ISSN: 10788956





Nature Medicine
Editorial
Nature Publishing Group, United States, Reino Unido
Tipo de documento: Article
Volumen: 29 Número: 9
Páginas: 2358
WOS Id: 001060207700001
ID de PubMed: 37635157
imagen Green Published, hybrid

MÉTRICAS