GLP-1 RECEPTOR AGONISTS AND CARDIOVASCULAR OUTCOMES IN PATIENTS WITH CORONARY PLAQUE: A REAL-WORLD PROPENSITY-MATCHED ANALYSIS

Therapeutic Area

CVD Prevention – Primary and Secondary

Background

Atherosclerotic plaque burden remains a major driver of cardiovascular events in patients with coronary artery disease. Glucagon-like peptide-1 (GLP-1) receptor agonists have shown potential cardiovascular benefits, but their impact on patients with established plaque remains under investigation. This study assesses the effect of GLP-1 therapy in patients with confirmed coronary plaque.

Methods

Using TriNetX, a federated electronic medical record network from January 1, 2022 to December 31, 2024, we identified two propensity-matched cohorts with documented coronary plaque: those who received GLP-1 analogues (n=24,648) and those who did not (n=24,648). Inclusion required both imaging consistent with plaque (e.g., coronary CTA, angiography, calcium scoring) and diagnostic codes for atherosclerosis. Outcomes analyzed over 1-year follow-up included major adverse cardiovascular events (MACE), myocardial infarction (MI), inpatient hospitalizations, and lipid panel values (LDL, total cholesterol, non-HDL, triglycerides).

Results

Compared to controls, GLP-1 users had significantly lower risks of:

• MACE (34.3% vs. 41.9%; OR 0.725, 95% CI 0.699–0.751, p<0.001)

• Myocardial infarction (13.9% vs. 20.8%; OR 0.615, 95% CI 0.586–0.644, p<0.001)

• Inpatient visits (22.8% vs. 28.7%; OR 0.731, 95% CI 0.702–0.761, p<0.001)

Survival analysis demonstrated higher 1-year event-free survival in the GLP-1 group across all outcomes. GLP-1 users also had modestly improved lipid profiles, including lower LDL (70.8 vs. 73.6 mg/dL), total cholesterol (142.8 vs. 145.8 mg/dL), and non-HDL cholesterol (98.3 vs. 99.9 mg/dL). Although triglycerides remained higher in the GLP-1 group at 1 year (149.8 vs. 139.4 mg/dL), they showed a greater improvement from baseline, with a decrease of 14.2 mg/dL compared to a 5.4 mg/dL increase in the non-GLP-1 group.

Conclusions

Among patients with confirmed coronary plaque, GLP-1 therapy is associated with substantial reductions in adverse cardiovascular outcomes and improvements in lipid parameters. These findings support the cardiovascular protective role of GLP-1 analogues in high-risk atherosclerotic populations.