title: Addition of clopidogrel to aspirin in 45,852 patients with acute myocardial infarction: randomised placebo-controlled trial.
abstract: BACKGROUND
  Despite improvements in the emergency treatment of myocardial infarction (MI), early mortality and morbidity remain high. The antiplatelet agent clopidogrel adds to the benefit of aspirin in acute coronary syndromes without ST-segment elevation, but its effects in patients with ST-elevation MI were unclear.
  
  
  METHODS
  45,852 patients admitted to 1250 hospitals within 24 h of suspected acute MI onset were randomly allocated clopidogrel 75 mg daily (n=22,961) or matching placebo (n=22,891) in addition to aspirin 162 mg daily. 93% had ST-segment elevation or bundle branch block, and 7% had ST-segment depression. Treatment was to continue until discharge or up to 4 weeks in hospital (mean 15 days in survivors) and 93% of patients completed it. The two prespecified co-primary outcomes were: (1) the composite of death, reinfarction, or stroke; and (2) death from any cause during the scheduled treatment period. Comparisons were by intention to treat, and used the log-rank method. This trial is registered with ClinicalTrials.gov, number NCT00222573.
  
  
  RESULTS
  Allocation to clopidogrel produced a highly significant 9% (95% CI 3-14) proportional reduction in death, reinfarction, or stroke (2121 [9.2%] clopidogrel vs 2310 [10.1%] placebo; p=0.002), corresponding to nine (SE 3) fewer events per 1000 patients treated for about 2 weeks. There was also a significant 7% (1-13) proportional reduction in any death (1726 [7.5%] vs 1845 [8.1%]; p=0.03). These effects on death, reinfarction, and stroke seemed consistent across a wide range of patients and independent of other treatments being used. Considering all fatal, transfused, or cerebral bleeds together, no significant excess risk was noted with clopidogrel, either overall (134 [0.58%] vs 125 [0.55%]; p=0.59), or in patients aged older than 70 years or in those given fibrinolytic therapy.
  
  
  CONCLUSIONS
  In a wide range of patients with acute MI, adding clopidogrel 75 mg daily to aspirin and other standard treatments (such as fibrinolytic therapy) safely reduces mortality and major vascular events in hospital, and should be considered routinely.
authors.affiliation: Clinical Trial Service Unit and Epidemiological Studies Unit (CTSU), Richard Doll Building, Old Road Campus, Oxford OX3 7LF, UK. zhengming.chen@ctsu.ox.ac.uk
authors.forename: Z M
authors.initials: ZM
authors.lastname: Chen
authors.forename: L X
authors.initials: LX
authors.lastname: Jiang
authors.forename: Y P
authors.initials: YP
authors.lastname: Chen
authors.forename: J X
authors.initials: JX
authors.lastname: Xie
authors.forename: H C
authors.initials: HC
authors.lastname: Pan
authors.forename: R
authors.initials: R
authors.lastname: Peto
authors.forename: R
authors.initials: R
authors.lastname: Collins
authors.forename: L S
authors.initials: LS
authors.lastname: Liu
mesh_terms: D000368:Aged; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000627:therapeutic use*; D001241:Aspirin / Q000627:therapeutic use*; D002681:China; D000077144:Clopidogrel; D004359:Drug Therapy, Combination; D004562:Electrocardiography; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D009203:Myocardial Infarction / Q000188:drug therapy* / Q000401:mortality; D010975:Platelet Aggregation Inhibitors / Q000627:therapeutic use*; D013988:Ticlopidine / Q000031:analogs & derivatives* / Q000627:therapeutic use; D016896:Treatment Outcome
chemical_list: D000894:Anti-Inflammatory Agents, Non-Steroidal; D010975:Platelet Aggregation Inhibitors; D000077144:Clopidogrel; D013988:Ticlopidine; D001241:Aspirin