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

Barry A. Borlaug, Dalane W. Kitzman, Melanie J. Davies, Søren Rasmussen, Eric Barros, Javed Butler, Mette Nygaard Einfeldt, G. Kees Hovingh, Daniél Vega Møller, Mark C. Petrie, Sanjiv J. Shah, Subodh Verma, Walter Abhayaratna, Fozia Z. Ahmed, Vijay Chopra, Justin Ezekowitz, Michael Fu, Hiroshi Ito, Małgorzata Lelonek, Vojtech MelenovskyJulio Núñez, Eduardo Perna, Morten Schou, Michele Senni, Peter van der Meer, Dirk Von Lewinski, Dennis Wolf, Mikhail N. Kosiborod*

*Corresponding author af dette arbejde

Publikation: Bidrag til tidsskriftTidsskriftartikelForskningpeer review

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Abstract

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 ≥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 × 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.
OriginalsprogEngelsk
TidsskriftNature Medicine
Vol/bind29
Udgave nummer9
Sider (fra-til)2358-2365
Antal sider8
ISSN1078-8956
DOI
StatusUdgivet - 2023

Bibliografisk note

Funding Information:
This trial was sponsored by Novo Nordisk and is registered with ClinicalTrials.gov ( NCT04788511 ). The sponsor took responsibility for activities related to trial conduct, data collection and statistical analysis. The authors are indebted to the trial participants, the investigators and trial site staff who conducted the trial. Administrative support and development of figures and tables were provided by C. McKeown and L. Ambrose of Apollo, OPEN Health Communications, and were funded by Novo Nordisk, in accordance with Good Publication Practice guidelines ( https://www.ismpp.org/gpp-2022 ). B.A.B. is supported, in part, by National Institutes of Health (NIH) grants R01 HL128526, R01 HL162828 and U01 HL160226 and by US Department of Defense grant W81XWH2210245. M.J.D. is supported by Leicester National Institute for Health Research (NIHR) Biomedical Research Centre, Leicester General Hospital. D.W.K. is supported, in part, by NIH grants U01AG076928, R01AG078153, R01AG045551, R01AG18915, P30AG021332, U24AG059624 and U01HL160272. S.V. is supported by the Canadian Institutes of Health Research and the Heart and Stroke Foundation of Canada and holds the Canada Research Chair in Cardiovascular Surgery. M.C.P. is supported by the British Heart Foundation Centre of Research Excellence Award (RE/13/5/30177 and RE/18/6/34217+). S.J.S. was supported by research grants from the NIH (U54 HL160273, R01 HL107577, R01 HL127028, R01 HL140731 and R01 HL149423). D.W. is a member of SFB1425, funded by the Deutsche Forschungsgemeinschaft (DFG, German Research Foundation).

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© 2023, The Author(s).

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