Article,
Semaglutide and NT-proBNP in Obesity-Related HFpEF Insights From the STEP-HFpEF Program
Contributors
Petrie, Mark Colquhoun
0000-0002-6333-9496
[1]
Borlaug, Barry A
0000-0001-9375-0596
[2]
Davies, Melanie Jane
0000-0002-9987-9371
[5]
[6]
Shah, Sanjiv Jayendra
0000-0002-5655-8201
[8]
Sharma, Kavita
0000-0003-4714-7854
[13]
Ezekowitz, Justin Adrian
0000-0002-2724-4086
[14]
Melenovsky, Vojtech
0000-0001-8921-7078
[16]
Lelonek, Malgorzata Lidia
0000-0003-0756-5541
[18]
Affiliations
- [1] University of Glasgow [NORA names: United Kingdom; Europe, Non-EU; OECD];
- [2] Mayo Clinic [NORA names: United States; America, North; OECD];
- [3] Baylor Scott & White Health [NORA names: United States; America, North; OECD];
- [4] University of Mississippi [NORA names: United States; America, North; OECD];
- [5] NIHR Leicester Biomedical Research Centre [NORA names: United Kingdom; Europe, Non-EU; OECD];
(... more)
Abstract
BACKGROUND: The glucagon-like peptide-1 receptor agonist, semaglutide, improved health status and reduced body weight in patients with obesity-related heart failure (HF) with preserved ejection fraction (HFpEF) in the STEP-HFpEF (Semaglutide Treatment Effect in People with Obesity and HFpEF) program. Whether benefits were due to mechanical unloading or effects on HF pathobiology is uncertain. OBJECTIVES: This study sought to determine if semaglutide 2.4 mg reduced N-terminal pro-B-type natriuretic peptide (NT-proBNP) in patients with obesity-related HFpEF and compare treatment responses by baseline NT-proBNP. METHODS: This was a prespecified secondary analysis of pooled data from 2 double-blind, placebo-controlled, randomized trials (STEP-HFpEF [Research Study to Investigate How Well Semaglutide Works in People Living With Heart Failure and Obesity] and STEP-HFpEF DM [Research Study to Look at How Well Semaglutide Works in People Living With Heart Failure, Obesity and Type 2 Diabetes]) testing effects of semaglutide in patients with obesity-related HFpEF. The main outcomes were change in NT-proBNP at 52 weeks and change in the dual primary endpoints of Kansas City Cardiomyopathy Questionnaire Clinical Summary Score and body weight by baseline NT-proBNP. RESULTS: In total, 1,145 patients were randomized. Semaglutide compared with placebo reduced NT-proBNP at 52 weeks (estimated treatment ratio: 0.82; 95% CI: 0.74-0.91; P = 0.0002). Improvements in health status were more pronounced in those with higher vs lower baseline NT-proBNP (estimated difference: tertile 1: 4.5 points, 95% CI: 0.8-8.2; tertile 2: 6.2 points, 95% CI: 2.4-10.0; tertile 3: 11.9 points, 95% CI: 8.1-15.7; P interaction = 0.02; baseline NT-proBNP as a continuous variable: P interaction = 0.004). Reductions in body weight were consistent across baseline NT-proBNP levels (P interaction = 0.21). CONCLUSIONS: In patients with obesity-related HFpEF, semaglutide reduced NT-proBNP. Participants with higher baseline NT-proBNP had a similar degree of weight loss but experienced larger reductions in HF-related symptoms and physical limitations with semaglutide than those with lower NT-proBNP.
