Pranjal Rai, Girish Bathla, Eishvauk Aggarwal, Huanwen Alvin Chen, Jay Kakadiya, Matthew K. McIntyre, Hamza A. Salim, Ahmed Y. Azzam, Muhammed Amir Essibayi, Vivek S Yedavalli, Majid Khan, Adam A. Dmytriw, David J Altschul, Jefferson O. Abaricia, Marco Colasurdo, Ajay Malhotra, Dheeraj Gandhi, Dhairya A. Lakhani
BACKGROUND: Asymptomatic carotid stenosis is a prevalent manifestation of atherosclerotic disease and, despite contemporary guideline-directed medical therapy, remains associated with downstream cerebrovascular events and mortality. Given the vascular and cardiometabolic benefits of glucagon-like peptide-1 receptor agonists (GLP-1As), we evaluated whether GLP-1A exposure is associated with lower long-term event rates in patients with asymptomatic carotid stenosis. METHODS: This retrospective study used the TriNetX US Collaborative Network. Adults (≥18 years) with carotid stenosis (January 1, 2016-September 30, 2025) were included; patients with prior/baseline cerebrovascular events and those undergoing carotid revascularization within 6 months were excluded to operationalize an asymptomatic cohort. GLP-1A exposure was defined as any GLP-1A use within 6 months following carotid stenosis diagnosis; non-exposed patients served as comparators. Cohorts were propensity score-matched 1:1, and outcomes were assessed using Kaplan-Meier and Cox proportional hazards models. RESULTS: After matching, 30,332 patients were included in each cohort. GLP-1A exposure was associated with lower hazards of ischemic stroke (HR 0.63/0.71/0.73 at 1/3/5 years; 5-year cumulative event probability 5.55% vs 6.85%), hemorrhagic stroke (HR 0.63/0.69/0.74; 2.04% vs 2.35%), large-vessel occlusion stroke (HR 0.70/0.77/0.81; 2.04% vs 2.27%), and all-cause mortality (HR 0.42/0.58/0.64; 17.11% vs 21.49%). The composite of ischemic stroke or mortality was also lower (HR 0.48/0.61/0.66; 20.88% vs 25.85% at 5 years) in the GLP-1A exposed cohort. CONCLUSIONS: In large real-world cohort with asymptomatic carotid stenosis, GLP-1A exposure was associated with lower hazards of stroke subtypes, large-vessel occlusion stroke, and mortality across 1-5 years. These observational findings warrant prospective validation to clarify causality and optimal integration into contemporary medical management.