Abstract
Introduction: While various antiplatelet regimens are currently available for secondary prevention after ischemic stroke, data comparing their efficacy and safety are scarce. We conducted a network meta-analysis investigating the efficacy and risk profile of each antiplatelet regimen including combination therapies for secondary prevention of recurrent stroke. Methods: PubMed and EMBASE were searched for reports on randomized controlled trials published between January 1, 1985, and July 21, 2020. Random-effects model was used for meta-analysis. Primary outcome was recurrent stroke after ischemic stroke and secondary outcomes was major bleeding. Results: 39 trials enrolling a total of 158,507 patients were eligible for our network meta-analysis. Patients were randomly allocated to receive aspirin, cilostazol, clopidogrel, dipyridamole, ticagrelor, ticlopidine, or combination of these antiplatelet agents in each study. In comparison to those who received aspirin monotherapy, the risk of recurrent stroke was significantly lower in patients who received cilostazol (odds ratio (OR), 0.65; 95% confidence interval (CI), 0.51-0.83), aspirin + ticagrelor (OR, 0.72; 95% CI, 0.62-0.83), aspirin + clopidogrel (OR, 0.73; 95% CI, 0.54-0.98) without significant heterogeneity (I2=45.1). Ticagrelor monotherapy did not demonstrate a significant difference in risk of recurrent stroke compared to clopidogrel monotherapy (OR, 1.02; 95% CI, 0.70-1.48). Aspirin and ticagrelor combination therapy did not demonstrate a significant difference in risk of recurrent stroke compared to aspirin and clopidogrel combination therapy (OR, 1.01; 95% CI, 0.74-1.39). Combination therapy of aspirin with clopidogrel or ticagrelor showed a higher risk of major bleeding compared to aspirin monotherapy (OR, 1.54; 95% CI, 1.30-1.84; OR, 2.93; 95% CI, 1.53-5.41, respectively). Conclusions: Ticagrelor and clopidogrel demonstrated similar efficacy and risk of major bleeding—as monotherapy and in combination with aspirin—when used for secondary prevention of recurrent stroke. Ticagrelor or clopidogrel in combination with aspirin showed lower risk of recurrent stroke but higher risk of major bleeding than aspirin monotherapy.
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