{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,30]],"date-time":"2026-07-30T10:14:21Z","timestamp":1785406461288,"version":"3.56.0"},"reference-count":22,"publisher":"MDPI AG","issue":"5","license":[{"start":{"date-parts":[[2026,5,21]],"date-time":"2026-05-21T00:00:00Z","timestamp":1779321600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000057","name":"National Institute of General Medical Sciences","doi-asserted-by":"crossref","award":["U54 GM104942"],"award-info":[{"award-number":["U54 GM104942"]}],"id":[{"id":"10.13039\/100000057","id-type":"DOI","asserted-by":"crossref"}]},{"award":["U54 GM104942"],"award-info":[{"award-number":["U54 GM104942"]}],"id":[{"id":"https:\/\/ror.org\/04q48ey07","id-type":"ROR","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Neurology International"],"abstract":"<jats:p>Background: Asymptomatic intracranial atherosclerotic arterial stenosis (ICAS) is an underrecognized entity for which vascular risk-factor optimization is the primary management strategy, with no current indication for routine antiplatelet therapy or endovascular intervention for primary stroke prevention. Glucagon-like peptide-1 receptor agonists (GLP-1RAs) reduce major adverse cardiovascular events, including stroke, in high-risk cardiometabolic populations, but their association with outcomes in asymptomatic ICAS is yet to be evaluated. The present study aims to evaluate the association between GLP-1RA use and cerebrovascular outcomes in adults with asymptomatic ICAS. Materials and Methods: We used the TriNetX US Collaborative Network (71 healthcare organizations) to identify adults (\u226518 years) with ICAS between 1 January 2016 and 31 December 2025, and excluded patients with prior cerebral infarction, intracranial hemorrhage, or cerebrovascular ischemic syndromes. Exposure was defined as initiation of any GLP-1 receptor agonist (lixisenatide, semaglutide, liraglutide, tirzepatide, dulaglutide) during the 6 months before or on the date of index ICAS diagnosis. Outcomes were assessed at 1 year, and included ischemic stroke, all-cause mortality, and a composite of ischemic stroke or mortality. Propensity-score matching (1:1) was performed, including demographics, vascular risk factors, comorbidities, antithrombotics, lipid\/diabetes therapies, and cardiometabolic laboratory\/physiologic measures. Results: Before matching, 1746 GLP-1RA users and 71,792 non-users met inclusion criteria; after matching, 1728 patients remained in each cohort. GLP-1RA use was associated with lower 1-year risk of ischemic stroke (4.40% vs. 6.10%; hazard ratio [HR] 0.70, 95% CI 0.52\u20130.95; p = 0.044), lower all-cause mortality (3.40% vs. 9.40%; HR 0.35, 95% CI 0.26\u20130.47; p &lt; 0.001), and lower composite outcome risk (7.50% vs. 15.00%; HR 0.48, 95% CI 0.39\u20130.59; p &lt; 0.001). Notably, these associations were observed despite matching for HbA1c, LDL cholesterol, BMI, and systolic blood pressure, suggesting potential effects beyond measured cardiometabolic risk profiles. Conclusions: In this large, propensity-matched cohort of adults with a-ICAS, GLP-1RA use was associated with lower ischemic stroke, all-cause mortality, and composite outcome at 1 year. These findings are hypothesis-generating and require further prospective studies to confirm this observation.<\/jats:p>","DOI":"10.3390\/neurolint18050098","type":"journal-article","created":{"date-parts":[[2026,5,27]],"date-time":"2026-05-27T10:19:52Z","timestamp":1779877192000},"page":"98","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Association of Glucagon-like Peptide-1 Receptor Agonist Use with Stroke and Mortality Outcomes in Asymptomatic Intracranial Atherosclerotic Disease: Propensity Score-Matched Real-World Analysis"],"prefix":"10.3390","volume":"18","author":[{"ORCID":"https:\/\/orcid.org\/0009-0008-3796-8273","authenticated-orcid":false,"given":"Pranjal","family":"Rai","sequence":"first","affiliation":[{"name":"Department of Radiology, Mayo Clinic, 200 1st Street Southwest, Rochester, MN 55902, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Daniel","family":"Mandel","sequence":"additional","affiliation":[{"name":"Department of Neurology, Rockefeller Neuroscience Institute, West Virginia University, Morgantown, WV 26506, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Girish","family":"Bathla","sequence":"additional","affiliation":[{"name":"Department of Radiology, Mayo Clinic, 200 1st Street Southwest, Rochester, MN 55902, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0007-3645-4054","authenticated-orcid":false,"given":"Vidhi","family":"Dhaduk","sequence":"additional","affiliation":[{"name":"Shantabaa Medical College and General Hospital, Amreli 365601, Gujarat, India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0006-1660-6180","authenticated-orcid":false,"given":"Radhika","family":"Rajeev","sequence":"additional","affiliation":[{"name":"Department of Radiology, Massachusetts General Hospital, Harvard University, Boston, MA 02114, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0009-2075-6562","authenticated-orcid":false,"given":"Jay","family":"Kakadiya","sequence":"additional","affiliation":[{"name":"Government Medical College, Surat 395001, Gujarat, India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Huanwen Alvin","family":"Chen","sequence":"additional","affiliation":[{"name":"Department of Neurosurgery, University of Maryland Medical Center, Baltimore, MD 21201, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hamza A.","family":"Salim","sequence":"additional","affiliation":[{"name":"Department of Neuroradiology, MD Anderson Medical Center, Houston, TX 77030, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4256-0159","authenticated-orcid":false,"given":"Ahmed Y.","family":"Azzam","sequence":"additional","affiliation":[{"name":"Department of Neuroradiology, Rockefeller Neuroscience Institute, West Virginia University, Morgantown, WV 26506, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Muhammed Amir","family":"Essibayi","sequence":"additional","affiliation":[{"name":"Department of Neurological Surgery and Montefiore-Einstein Cerebrovascular Research Lab, Montefiore Medical Center, Albert Einstein College of Medicine, Bronx, NY 10461, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Brian","family":"Connolly","sequence":"additional","affiliation":[{"name":"Department of Neuroradiology, Rockefeller Neuroscience Institute, West Virginia University, Morgantown, WV 26506, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0000-2270-6854","authenticated-orcid":false,"given":"Marc","family":"Buzzelli","sequence":"additional","affiliation":[{"name":"Department of Neuroradiology, Rockefeller Neuroscience Institute, West Virginia University, Morgantown, WV 26506, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2450-4014","authenticated-orcid":false,"given":"Vivek S.","family":"Yedavalli","sequence":"additional","affiliation":[{"name":"Department of Radiology and Radiological Sciences, Johns Hopkins Medical Center, Baltimore, MD 21205, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Majid","family":"Khan","sequence":"additional","affiliation":[{"name":"Department of Radiology and Radiological Sciences, Johns Hopkins Medical Center, Baltimore, MD 21205, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0131-5699","authenticated-orcid":false,"given":"Adam A.","family":"Dmytriw","sequence":"additional","affiliation":[{"name":"Nuffield Department of Surgical Sciences, Medical Sciences Division, University of Oxford, Oxford OX1 1NF, UK"},{"name":"Neuroendovascular Program, Massachusetts General Hospital, Harvard University, Boston, MA 02114, USA"},{"name":"Neurointerventional & Neuroanalytics Consortium (NAN-C), School of Medicine, Toronto Metropolitan University, Toronto, ON M5B 2K3, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David J.","family":"Altschul","sequence":"additional","affiliation":[{"name":"Department of Neurological Surgery and Montefiore-Einstein Cerebrovascular Research Lab, Montefiore Medical Center, Albert Einstein College of Medicine, Bronx, NY 10461, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0004-9788-5913","authenticated-orcid":false,"given":"Matthew K.","family":"McIntyre","sequence":"additional","affiliation":[{"name":"Department of Neurosurgery, Oregon Health & Science University, Portland, OR 97239, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marco","family":"Colasurdo","sequence":"additional","affiliation":[{"name":"Department of Interventional Radiology, Oregon Health & Science University, Portland, OR 97239, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9223-6640","authenticated-orcid":false,"given":"Ajay","family":"Malhotra","sequence":"additional","affiliation":[{"name":"Department of Radiology, Yale New Haven Hospital, New Haven, CT 06510, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dheeraj","family":"Gandhi","sequence":"additional","affiliation":[{"name":"Department of Neurosurgery, University of Maryland Medical Center, Baltimore, MD 21201, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dhairya A.","family":"Lakhani","sequence":"additional","affiliation":[{"name":"Department of Neuroradiology, Rockefeller Neuroscience Institute, West Virginia University, Morgantown, WV 26506, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,5,21]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1287","DOI":"10.1212\/WNL.0b013e31828ab2ed","article-title":"Prevalence of stenoses and occlusions of brain-supplying arteries in young stroke patients","volume":"80","author":"Schminke","year":"2013","journal-title":"Neurology"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"663","DOI":"10.1161\/STROKEAHA.113.003508","article-title":"Prevalence and Outcomes of Symptomatic Intracranial Large Artery Stenoses and Occlusions in China: The Chinese 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