Clinical Outcomes After Clopidogrel Versus Prasugrel Use in Endovascular Treatment of Unruptured Intracranial Aneurysms: A Propensity-Matched TriNetX Analysis

Background Endovascular treatment of unruptured intracranial aneurysms (UIAs) often requires dual antiplatelet therapy with aspirin and a P2Y12 inhibitor. Clopidogrel remains widely used, but variable bioactivation and high on-treatment platelet reactivity have prompted interest in alternatives such as prasugrel. We compared thromboembolic and hemorrhagic outcomes after clopidogrel versus prasugrel use in endovascular UIA treatment. Methods We queried the TriNetX Global Collaborative Network for adults with UIA who underwent endovascular treatment between 2016 and 2025 and received aspirin plus clopidogrel or prasugrel. Cohorts were matched 1:1 using propensity score matching based on demographics and comorbidities. Outcomes were assessed at 6 months and 1 year and reported as odds ratios (ORs) with 95% confidence intervals (CIs). Results Among 15,496 adults, 711 matched pairs were included. At 6 months, no significant differences were observed for in-stent thrombosis (OR 0.77, 95% CI 0.38?1.57; p=0.47), cerebral infarction (OR 1.04, 95% CI 0.75?1.46; p=0.80), cerebral hemorrhage (OR 1.07, 95% CI 0.80?1.44; p=0.65), or gastrointestinal hemorrhage (OR 0.84, 95% CI 0.43?1.64; p=0.61). Findings remained nonsignificant at 1 year. Conclusions In this propensity-matched TriNetX analysis, clopidogrel and prasugrel were not associated with significant differences in thromboembolic or hemorrhagic outcomes after endovascular UIA treatment. Prasugrel may be a reasonable alternative P2Y12 inhibitor in selected patients, including those with suspected or documented clopidogrel non-response.