Abstract 4369285: Lower Risk of Cardiovascular Events in Patients with Heart Failure Initiated on Semaglutide 2.4 mg in the Real-world: Results from the SCORE-HF Study (Semaglutide Effects on Cardiovascular Outcomes in People with Overweight or Obesi

Background: In a prespecified analysis of the SELECT trial, semaglutide 2.4 mg reduced major adverse cardiovascular events (MACE) and heart failure (HF) composite outcomes in patients with established cardiovascular disease, overweight/obesity, and prevalent HF without diabetes. However, real-world evidence on the effectiveness of semaglutide 2.4 mg in reducing MACE and HF outcomes among patients with HF remains limited. Research Questions: To evaluate the associations between semaglutide 2.4 mg use and the risk of MACE and HF outcomes, respectively, among U.S. adults with overweight/obesity and HF but no diabetes in routine clinical practice using real-world data. Methods: Patients aged ≥45 years with overweight/obesity and HF but no diabetes were identified from a large claims database linked to clinical and laboratory data (Komodo Research Data). A propensity score model including 64 variables was used to match patients (1:2) who did and did not initiate semaglutide 2.4 mg (6/2021-12/2024). Hazard ratios for semaglutide 2.4 mg use vs. non-use were derived using Cox proportional hazards models for the revised 3-point MACE (myocardial infarction, stroke, and all-cause mortality), revised 5-point MACE (including revised 3-point MACE, hospitalization for HF, and coronary revascularization), 3-point MACE and 5-point MACE (replacing all-cause mortality with cardiovascular [CV]-related mortality), and 3-point HF outcome (hospitalization for HF, urgent visit for HF, and CV-related mortality). Results: After matching, 8,617 patients who initiated semaglutide 2.4 mg and 17,234 non-users were included; characteristics were well-balanced (standardized mean difference <0.1 for all). Compared with non-use, semaglutide 2.4 mg use was associated with a lower risk of revised 5-point MACE (hazard ratio [HR]: 0.58, 95% confidence interval [CI]: 0.49 – 0.68), revised 3-point MACE (HR: 0.38, 95% CI: 0.28 – 0.50), 5-point MACE (HR: 0.61, 95% CI: 0.52 – 0.72), 3-point MACE (HR: 0.43, 95% CI: 0.31 – 0.58), and 3-point HF (HR: 0.65, 95% CI: 0.55 – 0.76) (all p < 0.001). Semaglutide 2.4 mg use was also associated with lower risk of MI, stroke, hospitalization for HF, all-cause mortality, and CV-related mortality, compared to non-use. Conclusion: In this real-world study of U.S. patients with overweight/obesity and HF but no diabetes, semaglutide 2.4 mg use was associated with significantly lower risks of MACE and HF outcomes.