Abstract Body: Background: Patients with obesity, without diabetes, and with coronary artery disease (CAD) remain at high residual cardiovascular risk despite statin therapy. Whether glucagon-like peptide-1 receptor agonists (GLP-1 RAs) are associated with sex-specific differences in incident cardiovascular outcomes in this population is unclear.
Hypothesis: Addition of GLP-1 RA therapy to statin therapy is associated with lower incident cardiovascular events compared with statin therapy alone, with differential associations by sex.
Methods: We performed a retrospective 1:1 propensity score-matched cohort study using the TriNetX research network. Adults with obesity, without diabetes, and with CAD receiving statin therapy were identified. The exposed cohort received GLP-1 RAs plus statins; the control cohort received statins alone, with no GLP-1 RA exposure. The index date was initiation of GLP-1 RA in the exposed cohort. Patients with prior outcomes were excluded. The mean follow-up was 18 months (range, 6-36 months). Sex-stratified outcomes included major adverse cardiovascular events (MACE: myocardial infarction, stroke, or all-cause mortality) along with individual outcomes, and heart failure. Odds ratios (ORs), 95% confidence intervals (CIs), and p values were reported.
Results: Among females (n=6,864), GLP-1 RA use was associated with lower odds of MACE (OR 0.271, 95% CI 0.214–0.344, p<0.0001), myocardial infarction (OR 0.343, 95% CI 0.234–0.502, p<0.0001), stroke (OR 0.380, 95% CI 0.257–0.562, p<0.0001), heart failure (OR 0.495, 95% CI 0.404–0.607, p<0.0001), and all-cause mortality (OR 0.154, 95% CI 0.111–0.214, p<0.0001). Among males (n=9,951), GLP-1 RA use was also associated with lower odds of MACE (OR 0.282, 95% CI 0.231–0.344, p<0.0001), myocardial infarction (OR 0.446, 95% CI 0.335–0.595, p<0.0001), stroke (OR 0.495, 95% CI 0.359–0.684, p<0.0001), heart failure (OR 0.541, 95% CI 0.451–0.649, p<0.0001), and all-cause mortality (OR 0.149, 95% CI 0.111–0.199, p<0.0001). Associations were observed in both sexes and were numerically stronger in females for cardiovascular outcomes.
Conclusions: In patients with obesity, without diabetes, and with CAD receiving statin therapy, GLP-1 RAs were associated with lower odds of incident MACE, myocardial infarction, stroke, heart failure, and all-cause mortality. Associations appeared more pronounced in females for several cardiovascular outcomes, though further studies are needed to confirm sex-specific differences.