(P178) SEMAGLUTIDE AND CARDIOVASCULAR OUTCOMES IN PEOPLE WITH OVERWEIGHT OR OBESITY AND HEART FAILURE: A PRE-SPECIFIED ANALYSIS FROM THE SELECT TRIAL

Background: The impact of glucagon like peptide-1 receptor agonist (GLP-1 RA), semaglutide on major adverse cardiovascular events (MACE; cardiovascular [CV] death, nonfatal myocardial infarction, or nonfatal stroke) and heart failure (HF) outcomes in people with HF is unknown.

METHODS AND RESULTS: Of the 17,604 participants (body mass index, ≥27 kg/m2) with pre-existing CV disease without diabetes (HbA1c < 6.5%) enrolled in the SELECT (Semaglutide Effects on Cardiovascular Outcomes in People With Overweight or Obesity) trial, 4,286 of them had an investigator-reported history of HF at randomization. In a pre-specified analysis, we examined the effects of once-weekly subcutaneous semaglutide 2.4 mg vs placebo on time-to-first-event of MACE, and a composite of CV death or worsening HF (HF hospitalization or urgent visit) among those with HF. Outcomes were also examined within subgroups of investigator-reported HF categories (heart failure with preserved ejection fraction, HFpEF; heart failure with reduced ejection fraction, HFrEF). Baseline clinical characteristics were similar across SELECT regardless of HF history. Semaglutide reduced the risk of both MACE and the composite of CV death or worsening HF [hazard ratio (95% confidence interval) 0.72 (0.60-0.87) and 0.79 (0.64-0.98), respectively vs. placebo], which was consistent with the effects observed in people without HF (interaction p-values >0.10) (Figure). People with HFpEF (n=2,273) and HFrEF (n=1,347) had comparable benefit from semaglutide for MACE (0.69 [0.51-0.91] and 0.66 [0.49-0.87], respectively) and the composite of CV death or worsening HF (0.75 [0.52-1.07] and 0.79 [0.58-1.07]).

Conclusion: In the SELECT trial, semaglutide 2.4 mg reduced the risk of MACE and CV death or worsening HF in people with and without HF, which was irrespective of HF subtype.