TY - JOUR
T1 - Semaglutide and NT-proBNP in Obesity-Related HFpEF
T2 - Insights From the STEP-HFpEF Program
AU - STEP-HFpEF Trial Committees and Investigators
AU - Petrie, Mark C.
AU - Borlaug, Barry A.
AU - Butler, Javed
AU - Davies, Melanie J.
AU - Kitzman, Dalane W.
AU - Shah, Sanjiv J.
AU - Verma, Subodh
AU - Jensen, Thomas Jon
AU - Einfeldt, Mette Nygaard
AU - Liisberg, Karoline
AU - Perna, Eduardo
AU - Sharma, Kavita
AU - Ezekowitz, Justin A.
AU - Fu, Michael
AU - Melenovský, Vojtěch
AU - Ito, Hiroshi
AU - Lelonek, Małgorzata
AU - Kosiborod, Mikhail N.
N1 - Publisher Copyright:
© 2024 The Authors
PY - 2024/7/2
Y1 - 2024/7/2
N2 - 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.
AB - 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.
KW - N-terminal pro–B-type natriuretic peptide
KW - heart failure with preserved ejection fraction
KW - obesity
KW - semaglutide
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U2 - 10.1016/j.jacc.2024.04.022
DO - 10.1016/j.jacc.2024.04.022
M3 - Article
C2 - 38819334
AN - SCOPUS:85194351500
SN - 0735-1097
VL - 84
SP - 27
EP - 40
JO - Journal of the American College of Cardiology
JF - Journal of the American College of Cardiology
IS - 1
ER -
