title: Effects of clopidogrel in addition to aspirin in patients with acute coronary syndromes without ST-segment elevation.
abstract: BACKGROUND
  Despite current treatments, patients who have acute coronary syndromes without ST-segment elevation have high rates of major vascular events. We evaluated the efficacy and safety of the antiplatelet agent clopidogrel when given with aspirin in such patients.
  
  
  METHODS
  We randomly assigned 12,562 patients who had presented within 24 hours after the onset of symptoms to receive clopidogrel (300 mg immediately, followed by 75 mg once daily) (6259 patients) or placebo (6303 patients) in addition to aspirin for 3 to 12 months.
  
  
  RESULTS
  The first primary outcome--a composite of death from cardiovascular causes, nonfatal myocardial infarction, or stroke--occurred in 9.3 percent of the patients in the clopidogrel group and 11.4 percent of the patients in the placebo group (relative risk with clopidogrel as compared with placebo, 0.80; 95 percent confidence interval, 0.72 to 0.90; P<0.001). The second primary outcome--the first primary outcome or refractory ischemia--occurred in 16.5 percent of the patients in the clopidogrel group and 18.8 percent of the patients in the placebo group (relative risk, 0.86; 95 percent confidence interval, 0.79 to 0.94; P<0.001). The percentages of patients with in-hospital refractory or severe ischemia, heart failure, and revascularization procedures were also significantly lower with clopidogrel. There were significantly more patients with major bleeding in the clopidogrel group than in the placebo group (3.7 percent vs. 2.7 percent; relative risk, 1.38; P=0.001), but there were not significantly more patients with episodes of life-threatening bleeding (2.2 percent [corrected] vs. 1.8 percent; P=0.13) or hemorrhagic strokes (0.1 percent vs. 0.1 percent).
  
  
  CONCLUSIONS
  The antiplatelet agent clopidogrel has beneficial effects in patients with acute coronary syndromes without ST-segment elevation. However, the risk of major bleeding is increased among patients treated with clopidogrel.
authors.forename: S
authors.initials: S
authors.lastname: Yusuf
authors.forename: F
authors.initials: F
authors.lastname: Zhao
authors.forename: S R
authors.initials: SR
authors.lastname: Mehta
authors.forename: S
authors.initials: S
authors.lastname: Chrolavicius
authors.forename: G
authors.initials: G
authors.lastname: Tognoni
authors.forename: K K
authors.initials: KK
authors.lastname: Fox
mesh_terms: D000208:Acute Disease; D000368:Aged; D001241:Aspirin / Q000627:therapeutic use*; D002318:Cardiovascular Diseases / Q000453:epidemiology / Q000401:mortality; D000077144:Clopidogrel; D004359:Drug Therapy, Combination; D004562:Electrocardiography; D005260:Female; D006470:Hemorrhage / Q000139:chemically induced; D006801:Humans; D008297:Male; D008875:Middle Aged; D017202:Myocardial Ischemia / Q000188:drug therapy*; D010975:Platelet Aggregation Inhibitors / Q000009:adverse effects / Q000627:therapeutic use*; D012307:Risk Factors; D013988:Ticlopidine / Q000009:adverse effects / Q000031:analogs & derivatives / Q000627:therapeutic use*
chemical_list: D010975:Platelet Aggregation Inhibitors; D000077144:Clopidogrel; D013988:Ticlopidine; D001241:Aspirin