Semaglutide and NYHA Functional Class in Obesity-Related Heart Failure With Preserved Ejection Fraction
Year: 2024
Type: article
Abstract: BACKGROUND: In the Semaglutide Treatment Effect in People with obesity and HFpEF (STEP-HFpEF) program, semaglutide improved heart failure (HF)-related symptoms, physical limitations, and exercise function, and reduced bodyweight in patients with obesity-related heart failure with preserved ejection fraction (HFpEF). Whether semaglutide improves functional status, as assessed by NYHA functional class, is unknown. OBJECTIVES: The goal of this study was to examine the effects of semaglutide on change in NYHA functional class over time. We also investigated the effects of semaglutide on HF-related symptoms, physical limitations, and bodyweight and other trial endpoints across baseline NYHA functional class categories. METHODS: This was a prespecified analysis of pooled data from 2 international, double-blind, randomized trials (STEP-HFpEF and STEP-HFpEF type 2 diabetes [STEP-HFpEF DM], comprising the STEP-HFpEF program), which collectively randomized 1,145 participants with obesity-related HFpEF to once-weekly semaglutide 2.4 mg or placebo for 52 weeks. The outcome of interest for this analysis was the change in NYHA functional class (baseline to 52 weeks). We also investigated the effects of semaglutide on the dual primary, confirmatory secondary, and selected exploratory endpoints according to baseline NYHA functional class. RESULTS: More semaglutide-treated than placebo-treated patients had an improvement in NYHA functional class (32.6% vs 21.5%, respectively; OR: 2.20 [95% CI: 1.62-2.99; P < 0.001]) and fewer semaglutide-treated patients experienced deterioration in NYHA functional class (2.09% vs 5.24%, respectively; OR: 0.36 [95% CI: 0.19-0.70; P = 0.003]) at 52 weeks. Semaglutide (vs placebo) improved the Kansas City Cardiomyopathy Questionnaire-Clinical Summary Score (KCCQ-CCS) across NYHA functional class categories; this was especially pronounced in those in NYHA functional classes III/IV (10.5 points [95% CI: 6.6-14.4 points]) vs NYHA functional class II (6.0 points [95% CI: 3.4-8.6 points]) (P interaction = 0.06). By contrast, the degree of reduction in bodyweight was similar with semaglutide vs placebo regardless of baseline NYHA functional class category (NYHA functional class II, -8.4% [95% CI: -9.4% to -7.3%]; NYHA functional classes III/IV, -8.3% [95% CI: -9.9% to -6.8%]; P interaction = 0.96). Semaglutide consistently improved 6-minute walking distance (6MWD), the hierarchical composite endpoint (death, HF events, differences in KCCQ-CSS, and 6MWD changes), and reduced C-reactive protein and N-terminal prohormone of brain natriuretic peptide across NYHA functional class categories (all P interactions = NS). CONCLUSIONS: In patients with obesity-related HFpEF, fewer semaglutide-treated than placebo-treated patients had a deterioration, and more had an improvement, in NYHA functional class at 52 weeks. Semaglutide consistently improved HF-related symptoms, physical limitations, and exercise function, and reduced bodyweight and biomarkers of inflammation and congestion in all NYHA functional class categories. Semaglutide-mediated improvements in health status were especially large in patients with NYHA functional classes III/IV. (Research Study to Look at How Well Semaglutide Works in People Living With Heart Failure and Obesity; NCT04788511) (Research Study to Look at How Well Semaglutide Works in People Living With Heart Failure, Obesity and Type 2 Diabetes; NCT04916470).
Institutions: University of Copenhagen, Herlev Hospital, Gentofte Hospital, University of Glasgow, Mayo Clinic, University of Mississippi Medical Center, University of Mississippi, Baylor Scott & White Research Institute, University of Leicester, NIHR Leicester Biomedical Research Centre, Wake Forest University Health Sciences, Wake Forest University, Northwestern University, St. Michael's Hospital, University of Toronto, Unity Health Toronto, University of Missouri–Kansas City, Novo Nordisk (Denmark), Saint Luke's Hospital
Language: English
Subfield: Cardiology and Cardiovascular Medicine
Field: Medicine
Domain: Health Sciences
Open Access status: hybrid
Estimated APC paid: $6,825
Funders: U.S. Department of Defense, Amgen, Bristol-Myers Squibb, Eli Lilly and Company, Pfizer, AstraZeneca, GlaxoSmithKline, Sanofi, Gilead Sciences, Edwards Lifesciences, Boston Scientific Corporation, LivaNova, Cytokinetics, Tenax Therapeutics, Impulse Dynamics, Moderna, Horizon Therapeutics, Novo Nordisk, National Institutes of Health, American Regent, National Institute on Aging, National Heart, Lung, and Blood Institute
Awards: Repurposing of Metormin for Older Patients with HFpEF, Precision Medicine for Dilated Cardiomyopathy—Novel Assessment of Cardiac Mechanics via Speckle Tracking Echocardiography to Identify Early Phenotypes, Exercise Intolerance in Older HFPEF Patients, Machine learning for the automated identification and tracking of rare myocardial diseases, REHAB-HF: A Trial of Rehabilitation Therapy in Older Acute Heart Failure Patients, HeartShare DeCODE-HF: Data translation center to Combine Omics, Deep phenotyping, and Electronic health records for Heart Failure subtypes and treatment targets, Wake Forest Claude D. Pepper OAIC - Renewal, Pepper OAIC Coordinating Center, Wake Forest Atrium HeartShare Clinical Center, Physical Rehabilitation for Older Patients with Acute HFpEF-The REHAB-HFpEF Trial
OpenAlex ID: W4399985802