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Glucagon-Like Peptide-1 Receptor Agonist Exposure and Long-Term Outcomes in Patients with Asymptomatic Carotid
Pranjal Rai1, Girish Bathla1, Eishvauk Aggarwal1
1From the Department of Radiology (P.R., G.B., E.A.), Mayo Clinic, 200 1st Street Southwest, Rochester, MN 55902; Department of Neurosurgery (H.A.C., D.G.), University of Maryland Medical Center, Baltimore, MD, USA; Department of Neuroradiology (J.K., H.A.S., A.Y.A., D.A.L.), Rockefeller Neuroscience Institute, West Virginia University, Morgantown, WV, USA; Department of Neurological Surgery (M.K.M., J.O.A.), Interventional Radiology (M.C.), Oregon Health & Science University, Portland, OR, USA; Department of Neuroradiology (H.A.S.), MD Anderson Medical Center, Houston, TX, USA; Department of Radiology and Radiological Sciences (H.A.S., V.S.Y., M.K.), Johns Hopkins Medical Center, Baltimore, Maryland, USA; Department of Neurological Surgery and Montefiore-Einstein Cerebrovascular Research Lab (A.Y.A., M.A.E., D.J.A.), Montefiore Medical Center, Albert Einstein College of Medicine, Bronx, NY, USA; Neuroendovascular Program (A.A.D.), Massachusetts General Hospital, Harvard University, Boston, MA, USA; Neurovascular Centre (A.A.D.), Departments of Medical Imaging and Neurosurgery, St Michael's Hospital, Toronto, ON, Canada and Department of Radiology (A.M.), Yale New Haven Hospital, New Haven, CT, USA.
Insights
Glucagon-like peptide-1 receptor agonists (GLP-1As) may reduce stroke and mortality risks in patients with asymptomatic carotid stenosis. This real-world study found GLP-1A exposure linked to significantly lower event rates over five years.
Area of Science:
- Cardiovascular Medicine
- Endocrinology
- Neurology
Background:
- Asymptomatic carotid stenosis is a common condition linked to atherosclerotic disease, posing risks for cerebrovascular events and mortality despite current treatments.
- Glucagon-like peptide-1 receptor agonists (GLP-1As) demonstrate known vascular and cardiometabolic benefits.
Purpose of the Study:
- To investigate the association between glucagon-like peptide-1 receptor agonist (GLP-1A) exposure and long-term event rates in patients diagnosed with asymptomatic carotid stenosis.
Main Methods:
- A retrospective analysis of adults (≥18 years) with carotid stenosis from January 1, 2016, to September 30, 2025, using the TriNetX US Collaborative Network.
- Exclusion criteria included prior/baseline cerebrovascular events and carotid revascularization within six months to define an asymptomatic cohort.
- Propensity score matching (1:1) compared GLP-1A exposed patients (use within six months of diagnosis) with non-exposed comparators, assessing outcomes via Kaplan-Meier and Cox proportional hazards models.
Main Results:
- The study included 30,332 propensity score-matched patients in each cohort (GLP-1A exposed vs. non-exposed).
- GLP-1A exposure was associated with significantly reduced hazards for ischemic stroke (5-year cumulative probability 5.55% vs. 6.85%), hemorrhagic stroke (2.04% vs. 2.35%), and large-vessel occlusion stroke (2.04% vs. 2.27%).
- All-cause mortality was notably lower in the GLP-1A exposed group (17.11% vs. 21.49% over 5 years), as was the composite of ischemic stroke or mortality (20.88% vs. 25.85%).
Conclusions:
- In a large real-world cohort of patients with asymptomatic carotid stenosis, GLP-1A exposure correlated with decreased risks of various stroke subtypes and mortality over a 1-5 year period.
- These observational findings suggest a potential benefit of GLP-1As in managing asymptomatic carotid stenosis.
- Further prospective validation is recommended to confirm causality and guide integration into clinical practice.
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.
