AIMS: To evaluate the association between semaglutide 2.4 mg and major adverse cardiovascular events (MACE) among adults with clinical atherosclerotic cardiovascular disease (ASCVD) and overweight/obesity without diabetes in real-world clinical practice.
MATERIALS AND METHODS: Adults aged ≥ 45 years with overweight/obesity and clinical ASCVD were identified from a United States database (2016-2024). Patients initiating semaglutide 2.4 mg were matched 1:2 with individuals not treated with semaglutide 2.4 mg through a propensity score model including > 70 demographic and clinical covariates. Primary outcomes were revised 3-point MACE (rMACE-3: myocardial infarction [MI], stroke, all-cause mortality) and revised 5-point MACE (rMACE-5: rMACE-3, heart failure [HF] hospitalisation, coronary revascularization). Secondary outcomes included 3-point MACE and 5-point MACE (replacing all-cause mortality with cardiovascular-related mortality) and HF composite outcomes; exploratory outcomes were incident type 2 diabetes (T2D), major adverse kidney events (MAKE) and major obesity-related adverse events (MORAE). Hazard ratios (HRs) and 95% confidence intervals (CIs) were estimated using Cox proportional hazards models.
RESULTS: The final sample comprised 38 308 patients with semaglutide 2.4 mg use propensity-score matched to 76 615 patients without. Over a mean follow-up of 8.6 months, semaglutide 2.4 mg significantly reduced the risk of rMACE-3 (HR: 0.55; 95% CI: 0.47-0.65), rMACE-5 (0.63; 0.56-0.71), MACE-3 (0.66; 0.56-0.78) and MACE-5 (0.69; 0.62-0.77). Semaglutide 2.4 mg also significantly reduced the risk of HF composite outcomes, T2D, MAKE and MORAE.
CONCLUSIONS: Semaglutide 2.4 mg was associated with a significantly reduced risk of MACE and other obesity-related outcomes, extending prior evidence of benefits to a broader clinical ASCVD population.
