Association between Semaglutide 2.4 mg and Risk of Cardiovascular Events in Patients with Heart Failure in the Real-world: Results from the SCORE-HF Study

Background Clinical trials have demonstrated that semaglutide 2.4 mg reduces cardiovascular events in patients with heart failure (HF) and overweight/obesity, but real-world evidence remains limited. Methods This retrospective study evaluated adults (≥45 years) with HF and overweight/obesity but without diabetes using a US database (2016–2024). Individuals initiating semaglutide 2.4 mg were propensity score–matched 1:2 to those not receiving semaglutide 2.4 mg. Primary outcomes were revised 3-point major adverse cardiovascular events (rMACE-3; myocardial infarction [MI], stroke, all-cause mortality) and revised 5-point MACE (rMACE-5; rMACE-3, HF hospitalization, coronary revascularization). Secondary outcomes included MACE-3 (MI, stroke, cardiovascular-related mortality), MACE-5 (MACE-3, HF hospitalization, coronary revascularization), 2-point HF (HF hospitalization, urgent HF visit), and 3-point HF (2-point HF, cardiovascular-related mortality). Results Among 8,617 individuals with semaglutide 2.4 mg use and 17,234 individuals without, the mean follow-up was 8.0 and 8.0 months, respectively. Semaglutide 2.4 mg was associated with a 62% lower risk of rMACE-3 (hazard ratio [HR] 0.38; 95% confidence interval [CI] 0.28–0.50), 42% lower risk of rMACE-5 (HR 0.58; 95% CI 0.49–0.68), 57% lower risk of MACE-3 (HR 0.43; 95% CI 0.31–0.58), and 39% lower risk of MACE-5 (HR 0.61; 95% CI 0.52–0.72) (all p<0.001). Risk reductions were consistent across HF composite outcomes (2-point HF: HR 0.71 [95% CI 0.60–0.84]; 3-point HF: HR 0.65 [95% CI 0.55–0.76]; both p<0.001). Conclusions Treatment with semaglutide 2.4 mg in patients with HF and overweight/obesity and without diabetes was associated with lower risks of MACE and HF outcomes, suggesting its potential role in comprehensive HF management.