Eur J Neurol. 2026 Jun;33(6):e70635. doi: 10.1111/ene.70635.
ABSTRACT
INTRODUCTION: To investigate the association of intracranial atherosclerotic disease (ICAD), alone and comorbid with cerebral small vessel disease (SVD), with ischemic or hemorrhagic events in patients receiving antithrombotic therapy.
PATIENTS AND METHODS: In this prospective, multicenter, observational study, baseline brain MRI was performed to assess SVD (white matter hyperintensities, cerebral microbleeds, lacunes, enlarged perivascular spaces [PVS]), nonlacunar infarcts, and ICAD. SVD burden was defined as SVD score > 2. ICAD was classified as normal-to-mild, moderate, and severe stenosis-to-occlusion. The outcomes were any ischemic event, ischemic stroke, major bleeding, intracranial hemorrhage, and all-cause mortality. We assessed associations of ICAD with outcomes via Cox regression and mediation analyses, adjusting for SVD burden.
RESULTS: Among 5250 patients (mean age: 71 ± 11 years, 33% women), 3947 (75%) received antiplatelets and 1304 (25%) anticoagulants at baseline. ICAD was normal-to-mild in 3781 (72%), moderate in 571 (11%), and severe-to-occluded in 894 (17%). SVD burden was observed in 1400 (27%). ICAD was associated with a higher frequency of non-lacunar infarcts and a lower frequency of PVS. There was no graded association between ICAD severity and SVD burden. During a median follow-up of 2 years, 278 ischemic events, 197 ischemic strokes, 97 major bleedings, 55 intracranial hemorrhages, and 217 deaths occurred. Severe-to-occluded ICAD independently increased the risk of any ischemic event (adjusted hazard ratio: 1.39 [1.03-1.86]) and mortality (2.01 [1.48-2.74]); coexisting SVD burden further increased the risk of all outcomes. ICAD directly affected ischemic events, while mortality was mainly driven by its additive interaction with SVD.
CONCLUSIONS: ICAD increases the risk of any ischemic events and, with comorbid SVD, contributes to hemorrhagic events and excess mortality.
PMID:42227730 | DOI:10.1111/ene.70635