title: Efficacy and safety of adding clopidogrel to aspirin on stroke prevention among high vascular risk patients: a meta-analysis of randomized controlled trials.
abstract: OBJECTIVE
  Whether clopidogrel should be added to aspirin for stroke prevention remained controversial for the risk of hemorrhagic complications. This meta-analysis was aimed to assess the efficacy and safety of adding clopidogrel to aspirin on stroke prevention in high vascular risk patients, and to provide evidence for a suitable duration of dual antiplatelet therapy.
  
  
  METHODS
  We searched PubMed, EMBase, OVID and Cochrane Central Register of Controlled Trials (up to June, 2013) for randomized controlled trials evaluating the efficacy and safety of clopidogrel plus aspirin versus aspirin alone in high vascular risk patients. Comparisons of stroke and hemorrhagic complications between treatment groups were expressed by the pooled Relative Risks (RRs) with 95% Confidence Intervals (CIs).
  
  
  RESULTS
  Fifteen trials with a total of 97692 intention-to-treat participants were included with duration of follow-up ranging from 7 days to 3.6 years. Dual antiplatelet therapy reduced all stroke by 21% (RR: 0.79, 95% CI: 0.73-0.85) with no evidence of heterogeneity across the trials (P = 0.27, I2 = 17%).The effects were consistent between short-term subgroup (≤1 month, RR: 0.76, 95% CI: 0.67-0.85) and long-term subgroup (≥3 months, RR: 0.81, 95% CI: 0.73-0.89). The risk of major bleeding was not significantly increased by dual antiplatelet therapy in short-term subgroup (RR: 1.11, 95% CI: 0.91-1.36), while significantly increased in long-term subgroup (RR: 1.52, 95% CI: 1.36-1.69). Long-term dual antiplatelet therapy substantially increased the risk of intracranial bleeding (RR: 1.76, 95% CI: 1.22-2.54).
  
  
  CONCLUSIONS
  This meta-analysis demonstrates that short-term combination of clopidogrel and aspirin is effective and safe for stroke prevention in high vascular risk patients. Long-term combination therapy substantially increases the risk of major bleeding and intracranial bleeding.
authors.affiliation: Department of Neurology, Sun Yat-sen Memorial Hospital, Sun Yat-Sen University, Guangzhou, Guangdong Province, China.
authors.forename: Shuying
authors.initials: S
authors.lastname: Chen
authors.affiliation: Department of Neurology, Affiliated Boji Hospital, Sun Yat-Sen University, Guangzhou, Guangdong Province, China.
authors.forename: Qingyu
authors.initials: Q
authors.lastname: Shen
authors.affiliation: Department of Neurology, Sun Yat-sen Memorial Hospital, Sun Yat-Sen University, Guangzhou, Guangdong Province, China.
authors.forename: Yamei
authors.initials: Y
authors.lastname: Tang
authors.affiliation: Department of Neurology, Sun Yat-sen Memorial Hospital, Sun Yat-Sen University, Guangzhou, Guangdong Province, China.
authors.forename: Lei
authors.initials: L
authors.lastname: He
authors.affiliation: Department of Neurology, Sun Yat-sen Memorial Hospital, Sun Yat-Sen University, Guangzhou, Guangdong Province, China.
authors.forename: Yi
authors.initials: Y
authors.lastname: Li
authors.affiliation: Department of Neurology, Guangdong General Hospital, Guangzhou, Guangdong Province, China.
authors.forename: Hui
authors.initials: H
authors.lastname: Li
authors.affiliation: Department of Neurology, Sun Yat-sen Memorial Hospital, Sun Yat-Sen University, Guangzhou, Guangdong Province, China.
authors.forename: Mei
authors.initials: M
authors.lastname: Li
authors.affiliation: Department of Neurology, Sun Yat-sen Memorial Hospital, Sun Yat-Sen University, Guangzhou, Guangdong Province, China.
authors.forename: Ying
authors.initials: Y
authors.lastname: Peng
mesh_terms: D001241:Aspirin / Q000009:adverse effects* / Q000494:pharmacology*; D000077144:Clopidogrel; D006470:Hemorrhage / Q000139:chemically induced / Q000150:complications; D006801:Humans; D016032:Randomized Controlled Trials as Topic / Q000379:methods*; D012306:Risk; D012449:Safety; D020521:Stroke / Q000150:complications / Q000517:prevention & control*; D013988:Ticlopidine / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000494:pharmacology
chemical_list: D000077144:Clopidogrel; D013988:Ticlopidine; D001241:Aspirin
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