Polled Analysis: Semaglutide Reduces Heart Failure Events in Obese Patients with HFpEF

Study Design and Population: This post-hoc pooled analysis combined data from four randomized, placebo-controlled trials (SELECT, FLOW, STEP-HFpEF, and STEP-HFpEF DM) involving 3,743 participants with heart failure and preserved or mildly reduced ejection fraction (HFpEF). The participants had various comorbidities including obesity, diabetes, and atherosclerotic cardiovascular disease. They were randomized to receive either semaglutide or placebo.

Main Findings: Semaglutide significantly reduced the risk of the composite endpoint of cardiovascular death or worsening heart failure events compared to placebo (HR 0.69, 95% CI 0.53–0.89, p=0.0045). It also reduced worsening heart failure events alone (HR 0.59, 95% CI 0.41–0.82, p=0.0019). However, no significant reduction in cardiovascular death alone was observed (HR 0.82, 95% CI 0.57–1.16, p=0.25). Semaglutide was generally well tolerated, with fewer serious adverse events compared to placebo.

Implications for Practice: These findings suggest semaglutide may be an effective therapy to reduce heart failure-related events in obese patients with HFpEF. Although semaglutide did not reduce cardiovascular death, its ability to lower the risk of heart failure hospitalizations makes it a potential therapeutic option for managing HFpEF in this population, a condition with limited treatment choices.

Reference: Kosiborod MN, et al. (2024). Semaglutide versus placebo in patients with heart failure and mildly reduced or preserved ejection fraction: a pooled analysis of the SELECT, FLOW, STEP-HFpEF, and STEP-HFpEF DM randomised trials. The Lancet. DOI: https://doi.org/10.1016/S0140-6736(24)01643-X