National Institute for Research of Metabolic and Cardiovascular Diseases
Published January 30, 2024 | Version v1
Journal article Open

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

Creators

  • 1. Department of Cardiovascular Medicine, Mayo Clinic, Rochester, MN, United States
  • 2. Department of Cardiovascular Medicine and Section on Geriatrics and Gerontology, Wake Forest University School of Medicine, Winston-Salem, NC, United States
  • 3. Diabetes Research Centre, University of Leicester, Leicester, United Kingdom
  • 4. NIHR Leicester Biomedical Research Centre, Leicester, United Kingdom
  • 5. ROR icon Novo Nordisk (Denmark)
  • 6. Baylor Scott and White Research Institute, Dallas, TX and Department of Medicine, University of Mississippi, Jackson, MS, United States
  • 7. University of Glasgow
  • 8. Division of Cardiology, Department of Medicine, Northwestern University Feinberg School of Medicine, Chicago, IL, United States
  • 9. Division of Cardiac Surgery, Li Ka Shing Knowledge Institute of St. Michael's Hospital, Unity Health Toronto, University of Toronto, Toronto, ON, Canada
  • 10. College of Health and Medicine, The Australian National University, Canberra, ACT, Australia
  • 11. Division of Cardiovascular Sciences, Faculty of Biology, Medicine and Health, University of Manchester, Manchester, UK
  • 12. Clinical Cardiology, Heart Failure and Research, Max Super Specialty Hospital, Saket, New Delhi, India
  • 13. University of Alberta, Edmonton, AB, Canada
  • 14. Section of Cardiology, Department of Medicine, Sahlgrenska University Hospital-Ostra, Gothenburg, Sweden
  • 15. Department of General Internal Medicine 3, Kawasaki Medical School, Okayama, Japan
  • 16. Institute of Clinical and Experimental Medicine
  • 17. Department of Noninvasive Cardiology, Medical University of Lodz, Lodz, Poland
  • 18. Hospital Clínico Universitario de Valencia, INCLIVA, Universidad de Valencia, and CIBER Cardiovascular, Valencia, Spain
  • 19. Instituto de Cardiologia J. F. Cabral, Corrientes, Argentina
  • 20. Department of Cardiology, Herlev-Gentofte Hospital, University of Copenhagen, Herlev, Denmark
  • 21. Cardiovascular Department, ASST Papa Giovanni XXIII Hospital, Bergamo, Italy
  • 22. Department of Cardiology, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands
  • 23. Division of Cardiology, Medical University of Graz, Graz, Austria
  • 24. Cardiology and Angiology, Medical Center – University of Freiburg, Faculty of Medicine, University of Freiburg, Freiburg, Germany.
  • 25. Department of Cardiovascular Disease, Saint Luke's Mid America Heart Institute, University of Missouri-Kansas City School of Medicine, Kansas City, MO, USA

Description

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.

Notes

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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