Association of Peri-procedural Glucagon-Like Peptide-1 Receptor Agonist Exposure with Long-Term Outcomes After Carotid Artery Revascularization Procedures: A Propensity Score–Matched Analysis

BACKGROUND: Glucagon-like peptide-1 receptor agonists (GLP-1RAs) have been shown to improve cardiometabolic risk profiles, but their effect on cerebrovascular outcomes after carotid revascularization procedures such as carotid artery stenting (CAS) or carotid endarterectomy (CEA) remains unclear. These patients continue to face substantial long-term risks despite conventional medical therapy. METHODS: We performed a retrospective cohort study using de-identified electronic health record data from the TriNetX US Collaborative Network. Adults (≥18 years) with carotid artery stenosis who underwent CAS or CEA and had a GLP-1RA medication record on the procedure date or within the subsequent 90 days were identified using ICD-10 diagnosis and procedure codes. Separate cohorts for both procedures were constructed and propensity-score matched (PSM) 1:1 on demographics and comorbidities. Outcomes were assessed up to 5-years, and included ischemic strokes, all-cause mortality, and a composite outcome (ischemic stroke or death). Kaplan-Meier survival analyses with log-rank testing, and Cox-proportional hazards models were generated on the TriNetX platform. RESULTS: After matching, 443 patients were included in each CAS cohort and 633 patients in each CEA cohort. Following CAS, GLP-1RA exposure was associated with lower crude incidences and 5-year event probabilities of ischemic stroke (2.9% vs 5.9%; 21.30% vs 28.14%; HR, 0.436; 95% CI, 0.224-0.851), all-cause mortality (9.0% vs 19.0%; 18.65% vs 35.57%; HR, 0.531; 95% CI, 0.364-0.776), and the composite outcome (6.5% vs 10.6%; 37.61% vs 54.30%; HR, 0.546; 95% CI, 0.343-0.868). Following CEA, GLP-1RA exposure was likewise associated with lower ischemic stroke incidence and event probability (4.7% vs 9.8%; 15.64% vs 21.21%; HR, 0.533; 95% CI, 0.344-0.825), mortality (8.1% vs 18.8%; 16.81% vs 26.43%; HR, 0.569; 95% CI, 0.409-0.791), and composite outcome rates (8.4% vs 18.6%; 27.71% vs 41.76%; HR, 0.509; 95% CI, 0.367-0.704). CONCLUSIONS: In this retrospective PSM analysis, peri-procedural GLP-1RA exposure was associated with lower hazards of ischemic stroke, all-cause mortality, and the composite of ischemic stroke or death after CAS and CEA. These findings are hypothesis-generating and require confirmation in prospective studies.