title: Effects of combined aspirin and clopidogrel therapy on cardiovascular outcomes: a systematic review and meta-analysis.
abstract: BACKGROUND
  Aspirin and clopidogrel monotherapies are effective treatments for preventing vascular disease. However, new evidence has emerged regarding the use of combined aspirin and clopidogrel therapy to prevent cardiovascular events. We therefore performed a comprehensive systematic review and meta-analysis to evaluate the benefits and harms of combined aspirin and clopidogrel therapy on major cardiovascular outcomes.
  
  
  RESULTS
  We systematically searched Medline, Embase, the Cochrane Central Register of Controlled Trials, reference lists of articles, and proceedings of major meetings to identify studies to fit our analysis. Eligible studies were randomized controlled trials assessing the effect of combined aspirin and clopidogrel therapy compared with aspirin or clopidogrel monotherapy. We identified 7 trials providing data with a total of 48248 patients. These studies reported 5134 major cardiovascular events, 1626 myocardial infarctions, 1927 strokes, and 1147 major bleeding events. Overall, the addition of aspirin to clopidogrel therapy as compared to single drug therapy resulted in a 9% RR reduction (95%CI, 2 to 17) in major cardiovascular events, 14% RR reduction (95%CI, 3 to 24) in myocardial infarction, 16% RR reduction (95%CI, 1 to 28) in stroke, and 62% RR increase (95%CI, 26 to 108) in major bleeding events. We also present the data as ARR to explore net value as the reduction in cardiovascular events. Overall, we observed that combined therapy yielded 1.06% decrease (95%CI, 0.23% to 1.99%) in major cardiovascular events and 1.23% increase (95%CI, 0.52% to 2.14%) in major bleeding events.
  
  
  CONCLUSIONS
  Although the addition of aspirin to clopidogrel resulted in small relative reductions in major cardiovascular events, myocardial infarction, and stroke, it also resulted in a relative increase in major bleeding events. In absolute terms the benefits of combined therapy, a 1.06% reduction in major cardiovascular events, does not outweigh the harms, a 1.23% increase in major bleeding events.
authors.affiliation: Department of Health Statistics, Second Military Medical University, Shanghai, China.
authors.forename: Yu-Hao
authors.initials: YH
authors.lastname: Zhou
authors.forename: Xin
authors.initials: X
authors.lastname: Wei
authors.forename: Jian
authors.initials: J
authors.lastname: Lu
authors.forename: Xiao-Fei
authors.initials: XF
authors.lastname: Ye
authors.forename: Mei-Jing
authors.initials: MJ
authors.lastname: Wu
authors.forename: Jin-Fang
authors.initials: JF
authors.lastname: Xu
authors.forename: Ying-Yi
authors.initials: YY
authors.lastname: Qin
authors.forename: Jia
authors.initials: J
authors.lastname: He
mesh_terms: D001241:Aspirin / Q000627:therapeutic use*; D002318:Cardiovascular Diseases / Q000150:complications / Q000188:drug therapy* / Q000517:prevention & control; D000077144:Clopidogrel; D004359:Drug Therapy, Combination / Q000009:adverse effects; D006470:Hemorrhage / Q000139:chemically induced; D006801:Humans; D009203:Myocardial Infarction / Q000517:prevention & control; D016032:Randomized Controlled Trials as Topic; D020521:Stroke / Q000517:prevention & control; D013988:Ticlopidine / Q000031:analogs & derivatives* / Q000627:therapeutic use; D016896:Treatment Outcome
chemical_list: D000077144:Clopidogrel; D013988:Ticlopidine; D001241:Aspirin