Dual Antiplatelet Therapy After Ischemic Stroke Stratified by Intracranial or Extracranial Atherosclerotic Stenosis

Objective This objective of this study was to assess the efficacy and safety of clopidogrel plus aspirin for acute mild stroke or high‐risk transient ischemic attack (TIA) stratified by the status of symptomatic intracranial atherosclerotic stenosis (ICAS) or extracranial atherosclerotic stenosis (ECAS). Methods The study was a subgroup analysis of a randomized clinical trial. Participants with mild ischemic stroke or TIA were assigned to receive either clopidogrel plus aspirin or aspirin monotherapy. Participants were categorized into 4 groups by the status of symptomatic ICAS or ECAS: ICAS + ECAS group, only ECAS group, only ICAS group, and no stenosis group. The primary efficacy end point was any new stroke and the primary safety end point was moderate‐to‐severe bleeding within 90 days. Results The study enrolled 5,664 patients. Compared with other groups, the ICAS + ECAS group had a higher risk of recurrent stroke within 90 days (no stenosis = 5.7%; only ICAS = 7.2%; only ECAS = 10.3%; and ICAS + ECAS = 13.2%; p < 0.001). Although clopidogrel plus aspirin showed a numerically lower recurrence risk versus aspirin alone, no significant treatment effect difference emerged across the 4 groups. No significant interaction between antiplatelet therapy and the status of symptomatic ICAS or ECAS for recurrent stroke and moderate‐to‐severe bleeding was identified. Interpretation For acute mild ischemic stroke or TIA, although patients with both symptomatic ICAS and ECAS exhibited an elevated risk of recurrent stroke than other patients, no interaction effect between antiplatelet therapy and the status of symptomatic ICAS or ECAS for the risk of new stroke and moderate‐to‐severe bleeding was observed. ANN NEUROL 2025