AHA Scientific Sessions 2026 Abstract · Nov 2, 2026
Glucagon-Like Peptide-1 Receptor Agonists and Stroke Incidence in Carotid Artery Stenosis
By Jacobs J, Herbst W, Tsakiris E et al.
Background: Glucagon-like Peptide-1 Receptor Agonists (GLP-1RAs) offer benefits beyond glycemic control, with large, randomized trials establishing significant cardiovascular and neurovascular protection. However, no study has examined the efficacy of GLP-1RAs in a cohort of patients diagnosed with carotid artery stenosis (CAS), a population at elevated cerebrovascular risk. This study aims to quantify the capacity of GLP-1RAs to protect against stroke in this high-risk population. Methods: Using the TriNetX US Collaborative Network (June 2021-June 2026), we identified adults (>18 years) with CAS who initiated a GLP-IRA after their CAS diagnosis and compared them to patients with CAS who never received a GLP-1RA. The GLP-1RA cohort was restricted to patients whose BMI remained between 30-35 kg/m ² on GLP-1RA initiation and a year after GLP-1RA initiation to mitigate effects of weight loss. Cohorts were propensity score matched on demographics (age at index, gender, race), comorbidities (BMI, HTN, MI, atherosclerotic disease, peripheral vascular disease, HF, atrial fibrillation and flutter, valvular disease, T2DM, obesity, hypothyroidism, CAS laterality, CKD stage, OSA, smoking, alcohol-related disorders), and medication (statins, beta blockers, ACE-I/ARB, calcium channel blockers, antiplatelets, anticoagulants, antihemorrhagics). The outcomes ischemic stroke, transient ischemic attack (TIA), hemorrhagic stroke, carotid revascularization procedure, all-cause mortality, and major adverse cardiovascular events (MACE) were assessed over a 5-year follow-up period using Kaplan-Meier survival analysis with hazard ratios reported. Results: After propensity score matching, 7,583 pairs were identified. Cohorts were well balanced on all characteristics (SMD <0.1), with similar age at index (66.8 ± 9.4 vs. 67.0 ± 11.0 years) and sex distribution (49.6% vs. 49.7% male) between the GLP-1RA and no GLP-1RA groups, respectively. GLP-1RA use was associated with significantly lower rates of ischemic stroke (HR 0.79, 95% CI 0.66-0.94, p<0.01), hemorrhagic stroke (HR 0.64, 95% CI 0.48-0.85, p <0.01), carotid revascularization (HR 0.67, 95% CI 0.50-0.89, p<0.01), all-cause mortality (HR 0.41, 95% CI 0.36-0.47, p<0.01), and a composite MACE endpoint (HR 0.80, 95% CI 0.70-0.91, p<0.01). Conclusions: In this large propensity-matched retrospective cohort, GLP-1RA use was associated with reduced rates of neurovascular events, carotid disease progression, and mortality among patients with carotid artery stenosis whose BMI category did not change over the study period. These findings support prospective investigation of GLP-1RAs as stroke preventative tools in this population.