Article Impact Level: HIGH Data Quality: STRONG Summary of The Lancet, 404(10454), 773–786. https://doi.org/10.1016/S0140-6736(24)01498-3 Prof. John Deanfield et al.
Points
- The SELECT trial, a multinational, randomized, double-blind, placebo-controlled phase 3 study, evaluated the effects of semaglutide, a GLP-1 receptor agonist, on cardiovascular outcomes in patients with atherosclerotic cardiovascular disease, particularly those with a history of heart failure.
- The trial included 17,604 patients with a mean age of 61.6 years and a mean BMI of 33.4 kg/m², with 24.3% having a history of heart failure at enrollment.
- Semaglutide significantly reduced the risk of major adverse cardiovascular events (MACE) compared to placebo, with a hazard ratio (HR) of 0.72 for MACE, 0.76 for cardiovascular death, and 0.81 for all-cause mortality.
- The benefits of semaglutide were observed across both subtypes of heart failure (preserved and reduced ejection fraction), although absolute event rates were higher in the reduced ejection fraction group.
- The results suggest that semaglutide can significantly impact treatment approaches for patients with cardiovascular conditions and obesity, offering consistent benefits across various demographic and clinical subgroups.
Summary
In the context of the SELECT trial, a multinational, randomized, double-blind, placebo-controlled, phase 3 study, the effects of semaglutide, a GLP-1 receptor agonist, were evaluated for their impact on cardiovascular outcomes in patients with atherosclerotic cardiovascular disease, specifically focusing on those with a history of heart failure. The trial enrolled adults aged 45 years and older with a body mass index (BMI) of at least 27 kg/m2, administering the treatment via a graduated dosing regimen over 16 weeks, culminating in a weekly dose of 2.4 mg of semaglutide or a placebo. The primary analysis focused on the incidences of major adverse cardiovascular events (MACE) and other heart failure-related outcomes across various subgroups, including heart failure with preserved or reduced ejection fraction.
The study’s findings, drawn from a cohort of 17,604 patients with a mean age of 61.6 years and a mean BMI of 33.4 kg/m2, revealed that 24.3% had a history of heart failure at enrollment. Semaglutide showed a significant reduction in cardiovascular risks compared to placebo. Specifically, the hazard ratios (HR) for MACE were notably lower in the semaglutide group (HR 0.72, 95% CI 0.60–0.87), with similar improvements noted for cardiovascular death (HR 0.76, 95% CI 0.59–0.97) and all-cause mortality (HR 0.81, 95% CI 0.66–1.00). These benefits extended across both heart failure subtypes, though absolute event rates were higher in the reduced ejection fraction group.
This analysis underscores the efficacy of semaglutide in reducing MACE and heart failure-related complications in patients with underlying cardiovascular conditions and obesity, regardless of the subtype of heart failure. These results highlight the potential for semaglutide to significantly impact treatment paradigms, offering a non-discriminatory benefit across a broad demographic and clinical spectrum, including variations in age, sex, BMI, and heart failure severity.
Link to the article: https://www.thelancet.com/journals/lancet/article/PIIS0140-6736(24)01498-3/fulltext
References Deanfield, J., Verma, S., Scirica, B. M., Kahn, S. E., Emerson, S. S., Ryan, D., Lingvay, I., Colhoun, H. M., Plutzky, J., Kosiborod, M. N., Hovingh, G. K., Hardt-Lindberg, S., Frenkel, O., Weeke, P. E., Rasmussen, S., Goudev, A., Lang, C. C., Urina-Triana, M., Pietilä, M., … Tornøe, C. W. (2024). Semaglutide and cardiovascular outcomes in patients with obesity and prevalent heart failure: A prespecified analysis of the SELECT trial. The Lancet, 404(10454), 773–786. https://doi.org/10.1016/S0140-6736(24)01498-3
