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1. Patients assigned to semaglutide reported reduced major adverse cardiovascular events, regardless of heart failure subtype.

2. Benefits were consistent across baseline characteristics such as age, BMI, and diuretic use.

Evidence Rating Level: 1 (Excellent)

Study Rundown: Semaglutide is known to reduce the risk of major adverse cardiovascular events (MACE) in overweight and obese patients; however, its effect on patients with atherosclerotic cardiovascular disease and heart failure remains unclear. This double-blind randomized controlled trial aimed to evaluate the safety and efficacy of once-weekly semaglutide, a GLP-1 receptor agonist, in patients with cardiovascular disease, with or without heart failure. The primary outcome of this study was the occurrence of MACE, while a key secondary outcome was the composite of cardiovascular death, hospitalization, or urgent hospital visits due to heart failure. According to study results, semaglutide reduced MACE and heart failure-related outcomes across different heart failure subtypes compared to placebo. This study was strengthened by a randomized design with a relatively large sample size, thus adding to the validity of the findings.

Click to read the study in The Lancet

Relevant Reading: Semaglutide and Cardiovascular Outcomes in Obesity without Diabetes

In-depth [randomized controlled trial]: Between Oct 31, 2018, and Mar 31, 2021, 17 604 patients were assessed for eligibility in 41 countries. Included were patients ≥ 45 years old with a BMI ≥ 27 kg/m² and established cardiovascular disease. Altogether, 8803 patients in the semaglutide group and 8801 patients in the placebo group were included in the final analysis. The mean patient age was 61.6 years (standard deviation [SD] 8.9) with the mean BMI being 33.4 kg/m2 (SD 5.0). The primary outcome of MACE was reduced with semaglutide compared to placebo for all outcome measures in patients with heart failure (hazard ratio [HR] 0.72 for MACE; HR 0.76 for cardiovascular death; HR 0.81 for all-cause death; p>0.19). The secondary outcome of cardiovascular death, hospitalization, or urgent hospital visits for heart failure was also lower in the semaglutide group, with consistent benefits regardless of heart failure classification. Findings from this study suggest that semaglutide can reduce cardiovascular events in patients with atherosclerotic disease and obesity.

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