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Background  The safety and long‐term outcome of systemic thrombolysis in patients receiving antiplatelet medications remain subjects of great clinical significance. The objective of this meta‐analysis was to determine how prestroke antiplatelet therapy affects the risks and benefits of intravenous thrombolysis in patients with acute ischemic stroke.    Methods and Results  A dual‐reviewer search was conducted in PubMed and  EMBASE  databases through November 2015, from which 19 studies involving a total of 108 588 patients with acute ischemic stroke were identified based on preset inclusion criteria. Information on study designs, patient characteristics, exposures, outcomes, and adjusting confounders was extracted, and estimates were combined by using random‐effects models. The pooled crude estimates suggested that taking long‐term antiplatelet medications was associated with higher odds of symptomatic intracranial hemorrhage (odds ratio [OR] 1.70, 95%  CI  1.47–1.97) and death ( OR  1.46, 95%  CI  1.22–1.75) and lower odds of favorable functional outcomes ( OR  0.86, 95%  CI  0.80–0.93). However, the combined confounder‐adjusted results only confirmed a relatively weak positive association between prior antiplatelet therapy and symptomatic intracranial hemorrhage ( OR  1.21, 95%  CI  1.02–1.44) and demonstrated no significant relationship between antiplatelet therapy and the other 2 outcomes (favorable outcome  OR  1.09, 95%  CI  0.96–1.24; death  OR  1.02, 95%  CI  0.98–1.07). Subgroup analyses revealed that the associations between prestroke antiplatelet therapy and outcomes were dependent on time and antiplatelet agents.    Conclusions  Patients with acute ischemic stroke receiving long‐term antiplatelet medications were associated with greater risks of developing symptomatic intracranial hemorrhage after systemic thrombolysis. However, the overall independent association between prestroke antiplatelet therapy and unfavorable outcomes or mortality was insignificant.

Intravenous Thrombolysis for Acute Ischemic Stroke in Patients Receiving Antiplatelet Therapy: A Systematic Review and Meta‐analysis of 19 Studies