GLP-1 Receptor Agonists Added to Statin Therapy and Cardiovascular Outcomes in ASCVD A Propensity Score-Matched Cohort Study

Objective: To evaluate whether GLP-1 RA use added to statins is associated with lower all-cause mortality, myocardial infarction (MI), and ischemic stroke versus statin monotherapy in ASCVD patients with body mass index (BMI) 30 kg/m2. Approach and Results:Using the TriNetX Research Network (108 U.S. healthcare organizations), we identified ASCVD patients with BMI 30 kg/m2 on statins initiating a GLP-1 RA (n=166,278) versus statin-only controls (n=920,176). Propensity score matching on 34 covariates yielded 119,911 matched pairs followed 3 years. Prespecified analyses included a BMI 35 subgroup (62,385 pairs), four washout sensitivity analyses (30-120 days), and a familial hypercholesterolemia exclusion analysis (161,312 matched pairs). Results. GLP-1 RA use was associated with significantly lower all-cause mortality (4.0% vs. 7.5%; HR 0.479; 95% CI: 0.463-0.496; p<0.001), MI (HR 0.762; 95% CI: 0.737-0.788; p<0.001), and ischemic stroke (HR 0.671; 95% CI: 0.588-0.766; p<0.001). Benefits were consistent across the BMI 35 subgroup and all washout analyses. GLP-1 RA users were more likely to achieve LDL <55 mg/dL by risk analysis (17.1% vs. 15.3%; RR 1.118; p<0.001); the Kaplan-Meier analysis was non-significant (HR 1.007; p=0.538). Mortality benefit was preserved in the FH exclusion analysis. Conclusion: ASCVD patients with obesity on statins, GLP-1 RA use was associated with substantially lower mortality, MI, and stroke, suggesting GLP-1 RAs may serve as cardioprotective adjuncts to statin therapy in this population.