Comparative effectiveness and safety of antiplatelet drug regimens as secondary prevention after ischemic stroke or transient ischemic attack

Background: Different antiplatelet regimens are recommended for secondary prevention after ischemic stroke/transient ischemic attack (TIA), but studies on the comparative effectiveness and safety of each regimen in daily practice are lacking, particularly for the aspirin-clopidogrel regimen. Objectives: To assess the comparative effectiveness and safety of antiplatelet regimens as secondary prevention after ischemic stroke or TIA. Methods: A cohort study was conducted using data from the Clinical Practice Research Datalink. Patients aged ≥18 years with a first diagnosis of ischemic stroke or TIA in 1999-2013 who started an antiplatelet drug within 90 days after diagnosis were identified. Antiplatelet exposure was assessed during follow-up and categorized into aspirin-dipyridamole, aspirinonly, clopidogrel-only, aspirin-clopidogrel, others, and no use (discontinuers). The primary effectiveness outcome was ischemic stroke, and the safety outcome was major bleeding. Time-dependent Cox regression analysis was used to assess the associations between antiplatelet regimens and study outcomes, adjusted for confounders. Results: A total of 20,542 ischemic stroke/TIA patients were followed for a median duration of 2.4 years. There were 2916 (14.2%) ischemic stroke events during follow-up. Aspirin-only (HR 1.19, 95%CI 1.05-1.34) and clopidogrel-only (HR 1.21, 1.05-1.40) regimens were less effective compared to aspirin-dipyridamole in reducing the risk of ischemic stroke, while the aspirin-clopidogrel regimen was not statistically different (HR 1.13, 0.93-1.37). Clopidogrel-only (HR 1.41, 1.17-1.70) and aspirinclopidogrel (HR 1.66, 1.29-2.13) regimens were associated with a higher risk of major bleeding compared to aspirin-dipyridamole in patients without previous major bleeding. Conclusions: Compared to other antiplatelet regimens, an aspirin-dipyridamole regimen appears to have a favourable benefit-risk profile for secondary prevention after ischemic stroke/TIA