Poster Presentation Australian and New Zealand Obesity Society Annual Scientific Conference 2024

Once-weekly semaglutide in heart failure with preserved ejection fraction and obesity: main results from the STEP-HFpEF trial (#265)

Andrew Sindone 1 2 3 , Mikhail Kosiborod 4 , Steen Z Abildstrøm 5 , Barry A Borlaug 6 , Javed Butler 7 8 , Søren Rasmussen 5 , Melanie J Davies 9 10 , G. Kees Hovingh 5 11 , Dalane W Kitzman 12 , Marie L Lindegaard 5 , Daniél Vega Møller 5 , Sanjiv J Shah 13 , Marianne Bach Treppendahl 5 , Subodh Verma 14 , Mark C Petrie 15
  1. Department of Cardiology, Concord Repatriation General Hospital, Sydney, NSW, Australia
  2. The University of Sydney, Sydney, NSW, Australia
  3. Ryde Hospital, Eastwood, Sydney, NSW, Australia
  4. Department of Cardiovascular Disease, Saint Luke’s Mid America Heart Institute, University of Missouri-Kansas City School of Medicine, Kansas City, MO, USA
  5. Novo Nordisk A/S, Søborg, Denmark
  6. Department of Cardiovascular Medicine, Mayo Clinic, Rochester, MN, USA
  7. Baylor Scott and White Research Institute, Dallas, TX, USA
  8. Department of Medicine, University of Mississippi, Jackson, MS, USA
  9. Diabetes Research Centre, University of Leicester, Leicester, UK
  10. NIHR Leicester Biomedical Research Centre, Leicester, UK
  11. The Department of Vascular Medicine, Academic Medical Center, Amsterdam, The Netherlands
  12. Department of Cardiovascular Medicine and Section on Geriatrics and Gerontology, Wake Forest School of Medicine, Winston-Salem, NC, USA
  13. Division of Cardiology, Department of Medicine, Northwestern University Feinberg School of Medicine, Chicago, IL, USA
  14. Division of Cardiac Surgery, Li Ka Shing Knowledge Institute of St Michael’s Hospital, Unity Health Toronto, University of Toronto, Toronto, ON, Canada
  15. School of Cardiovascular and Metabolic Health, University of Glasgow, Glasgow, UK

Background and Aims: Obesity is a major risk factor for heart failure (HF) with preserved ejection fraction (HFpEF). To date, there are no approved therapies specifically targeting the obesity phenotype of HFpEF. STEP-HFpEF (NCT04788511) is a phase 3a trial investigating the effects of semaglutide on disease burden in people with HFpEF and obesity.

Methods: In this 52-week, double-blind trial, adults with HFpEF and body mass index (BMI) ≥30 kg/m2 were randomised 1:1 to once-weekly subcutaneous semaglutide 2.4 mg or placebo. Eligible participants had left ventricular ejection fraction (LVEF) ≥45%, New York Heart Association functional (NYHA) class II–IV, Kansas City Cardiomyopathy Questionnaire Clinical Summary Score (KCCQ-CSS) <90 points and ≥1 elevated filling pressure; or HF hospitalisation (within past year) plus ongoing diuretic use and/or structural echo abnormalities. Key exclusion criteria were prior/planned bariatric surgery, >5 kg change in body weight, recent (<30 days) cardiovascular event or recent HF hospitalisation, systolic blood pressure >160 mmHg and diabetes. Dual primary endpoints are change from baseline to 52 weeks in KCCQ-CSS and body weight.

Results: 529 participants (56.1% female, 95.8% White, median age 69 years) were randomised (83 sites, 13 countries). Median body weight was 105.1 kg, BMI 37.0 kg/m2; 66.0% (n=349) of participants had a BMI ≥35. Median baseline measurements were KCCQ-CSS 58.9 points, 6-minute walk distance 320 meters, high-sensitivity C-reactive protein 3.8 mg/L, LVEF 57% and N-terminal pro B-type natriuretic peptide 451 pg/mL. Overall, 52% had history of atrial fibrillation, 15.3% were hospitalised for HF, and 66.2% and 33.8% were in NYHA class II and III–IV, respectively. The majority of patients were treated with beta-blockers, diuretics and angiotensin enzyme/receptor inhibitors or blockers.

Conclusions: STEP-HFpEF will determine whether semaglutide 2.4 mg can improve symptoms, physical limitations and exercise function, plus weight loss, in patients with unmet need for additional therapies.