Semaglutide cuts obesity, improves Heart Failure symptoms in Atrial Fibrillation: JACC

A recent secondary analysis from the pooled data of the STEP-HFpEF (Heart Failure with Preserved Ejection Fraction) Program and STEP-HFpEF DM found that once a week's prescription of Semaglutide 2.4 mg has led to significant improvements in Heart failure-related symptoms and physical limitations in individuals with Atrial Fibrillation (AF) at the baseline than those without AF.

AF is frequently observed in individuals with HFpEF and leads to adverse outcomes in these individuals compared to those with normal sinus rhythm. Obesity is an important risk factor for the development and progression of HFpEF and AF. Previous research from the HFpEF and HFpEF DM trials showed that Semaglutide had better results in those with HF-related symptoms, physical limitations, exercise function, body weight, and obesity-related heart failure in obesity-related HFpEF. However, there is uncertainty on the efficacy of semaglutide in individuals with or without AF. Hence, researchers conducted a secondary analysis from the pooled data of the two trials to evaluate the baseline characteristics, and clinical features, of obesity-related HFpEF individuals with and without a history of AF. They also determined the efficacy of Semaglutide across various types of AF.

Individuals with heart failure, left ventricular ejection fraction ≥45%, body mass index ≥30 kg/m2, and Kansas City Cardiomyopathy Questionnaire–Clinical Summary Score (KCCQ-CSS) <90 points were randomized 1:1 to receive once-weekly semaglutide 2.4 mg or matching placebo for 52 weeks. The endpoints investigated based on the investigator-reported history of AF included the following:

• Primary - change in KCCQ-CSS and percent change in body weight Confirmatory

• Secondary - change in 6-minute walk distance, all-cause death, HF events, thresholds of change in KCCQ-CSS, and 6-minute walk distance; and C-reactive protein

• Exploratory endpoint - change in N-terminal pro–B-type natriuretic peptide

Based on the presence of AF, the responder analysis examined the improvements in the KCCQ-CSS score

Findings:

• Among 1145 individuals, 45% had a history of AF of different types Most of them with AF were older, male, with high levels of NTproBNP, were among the NYHA functional class III symptoms, and were taking more antithrombotics, beta-blockers, and diuretics.

• A significant improvement in the KCCQ-CSS score (11.5 vs 4.3 points was seen in the individuals with AF vs without AF A significant proportion of individuals with AF taking semaglutide reported ≥5-, ≥10-, ≥15-, and ≥20-point improvement in KCCQ-CSS than without AF and on placebo.

• Apart from these a consistent reduction in the CRP, NT-proBNP, and body weight was seen despite the AF status with semaglutide.

Thus, the study concluded that semaglutide was effective in improving HF-related symptoms and obesity-related heart failure with pronounced improvements in individuals with AF. Semaglutide proves to be a potential drug for improving heart failure symptoms and obesity in individuals with AF.

Further reading: Verma S, Butler J, Borlaug BA, et al. Atrial Fibrillation and Semaglutide Effects in Obesity-Related Heart Failure With Preserved Ejection Fraction: STEP-HFpEF Program. J Am Coll Cardiol. 2024;84(17):1603-1614. doi:10.1016/j.jacc.2024.08.023.