Semaglutide reduces heart failure events in patients with preserved ejection fraction

1. Patients in the semaglutide group reported fewer heart failure events than those in the placebo group.

2. No significant difference was observed between groups for cardiovascular death alone.

Evidence Rating Level: 1 (Excellent)

Study Rundown: Heart failure with preserved ejection fraction (HFpEF) is the most common form of heart failure, affecting patients with obesity, type 2 diabetes, and overweight. This condition is associated with a high risk of hospitalization and death. This pooled analysis of randomized controlled trials aimed to investigate whether semaglutide, a once-weekly injectable medication, reduces heart failure events in patients with HFpEF. The primary outcome of this study was the composite endpoint of cardiovascular death and the first worsening heart failure event, while a key secondary outcome was time to cardiovascular death alone. According to study results, semaglutide significantly reduced heart failure events but did not have a significant effect on rates of cardiovascular death. Although this study was well done, it was limited by its post-hoc design, pooling data from several trials rather than being a prospective trial.

Click to read the study in The Lancet

Relevant Reading: Semaglutide in Patients with Heart Failure with Preserved Ejection Fraction and Obesity

In-depth [systematic review and meta-analysis]: 22 282 patients were assessed for eligibility across the SELECT, FLOW, STEP-HFpEF, and STEP-HFpEF DM trials. Included were patients with a history of heart failure with preserved ejection fraction (HFpEF), obesity, type 2 diabetes, and cardiovascular disease. Altogether, 3743 patients (1914 in semaglutide and 1829 in placebo) were included in the final analysis. The primary outcome of cardiovascular death or first worsening heart failure event was significantly reduced in the semaglutide group compared to placebo (5.4% vs. 7.5%, hazard ratio [HR] 0.69, p=0.0045). The secondary outcome of worsening heart failure events alone was also lower in the semaglutide group (2.8% vs. 4.7%, HR 0.59, p=0.0019), while no significant difference was observed for cardiovascular death alone (3.1% vs. 3.7%, HR 0.82, p=0.25). This study’s findings suggest that semaglutide effectively reduces heart failure events in HFpEF, although its impact on cardiovascular death remains inconclusive.

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