Background: It is not well known whether prestroke antiplatelet agents (PAs) are associated with the subtypes of ischemic stroke. Methods: We screened patients in a hospital-based stroke registry. Patients who were admitted with a diagnosis of first-time ischemic stroke within 5 days of symptom onset were included. Ischemic stroke subtypes were classified in accordance with the Trial of ORG 10172 in Acute Stroke Treatment classification based on stroke mechanism: large-artery atherosclerosis (LA), cardioembolism (CE), small vessel occlusion (SVO), other determined (OC) or undetermined causes (UC). Multinomial logistic regression analyses were performed to evaluate the effect of PA on stroke subtypes before and after propensity score matching. Results: Among 3,025 patients, 748 (24.7%) were taking antiplatelet agents prior to stroke. After propensity score matching, 1,190 patients were ultimately included. The PA group was associated with strokes caused by SVO rather than LA in multinomial logistic regression of an unmatched dataset. However, multivariable analysis after propensity score matching demonstrated that PA use was associated with a higher probability of SVO and CE (OR 2.05, p < 0.001 and OR 1.62, p = 0.05, respectively) compared with LA. Conclusions: PAs were associated with specific index stroke subtypes.

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