Mandel, Daniel

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 (≥18 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 0.52–0.95; p = 0.044), lower all-cause mortality (3.40% vs. 9.40%; HR 0.35, 95% CI 0.26–0.47; p < 0.001), and lower composite outcome risk (7.50% vs. 15.00%; HR 0.48, 95% CI 0.39–0.59; p < 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.

Abstract Background and aims Interfacility transfers in rural areas are challenging due to limited ambulance and bed availability, image sharing issues, and access disparities. Regional transfers to strategically located primary stroke centers can reduce time to care, decrease helicopter use, support local economies, and conserve comprehensive stroke center (CSC) resources. This study established a primary stroke center as a regional transfer center (rSTC) within a telestroke network. Methods Over one year, stakeholders created regionally appropriate transfer workflows defined as patients without large vessel occlusion, low likelihood for neurosurgical decompression or critical illness within a rSTC and 4 surrounding centers. Continuous education and prospective case logs were maintained by the rSTC stroke coordinator and a retrospective chart review was conducted one year following the intervention period. Results Of 99 patients requiring transfer, 73 (73.7%) went to the rSTC, with an average stay of 2.1 days, no deaths, and no secondary CSC transfers. The remaining 26 (26.3%) were sent to the CSC, with longer stays (10.6 days) and higher mortality (23.1%). Transfers to the rSTC were faster (60 min vs. 188 min). Financial analysis showed significant EMS savings ($455,111) and local health system benefits ($730,000) when compared to the pre-intervention period. Conclusions Establishing an effective regional transfer model is possible with broad stakeholder engagement and regular network maintenance. rSTCs provide the right level of care for the right patient, improving efficient allocation of healthcare resources and avoiding futile transfers with costly admissions far from home while opening beds and reducing transfer times to CSCs. Conflict of interest Nothing to disclose