title: Incremental effect of clopidogrel on important outcomes in patients with cardiovascular disease: a meta-analysis of randomized trials.
abstract: OBJECTIVE
  To quantify the impact of clopidogrel plus aspirin on the individual outcomes of death, myocardial infarction, or stroke in patients with established cardiovascular disease, or in patients with multiple risk factors for vascular disease.
  
  
  BACKGROUND
  Randomized trials have demonstrated a reduction in composite outcomes when clopidogrel is added to aspirin therapy in patients with coronary artery disease; however, the magnitude of benefit on individual outcomes is unknown.
  
  
  METHODS
  We conducted a meta-analysis on randomized, controlled trials that compared aspirin plus clopidogrel with aspirin plus placebo for the treatment of coronary artery disease.
  
  
  RESULTS
  This analysis included five randomized trials (CURE, CREDO, CLARITY, COMMIT, and CHARISMA) in 79 624 patients. The incidence of all-cause mortality was 6.3% in the aspirin plus clopidogrel group versus 6.7% in the aspirin group (odds ratio [OR] 0.94; 95% CI 0.89, 0.99; p = 0.026). The incidence of myocardial infarction was 2.7% and 3.3% (OR 0.82; 95% CI 0.75, 0.89; p < 0.0001), and stroke was 1.2% and 1.4% (OR 0.82; 95% CI 0.73, 0.93; p = 0.002). Similarly, the incidence of major bleeding was 1.6% and 1.3% (OR 1.26; 95% CI 1.11, 1.41; p < 0.0001), and fatal bleeding was 0.28% and 0.27% (OR 1.04; 95% CI 0.76, 1.43; p = 0.79).
  
  
  CONCLUSIONS
  The addition of clopidogrel to aspirin results in a small reduction in all-cause mortality in patients with ST-elevation myocardial infarction and a modest reduction in myocardial infarction and stroke in patients with cardiovascular disease. The overall incidence of major bleeding however is increased, although there is no excess of fatal bleeds or hemorrhagic strokes.
authors: Department of Cardiovascular Medicine, Cleveland Clinic, Cleveland, Ohio, USA.
authors: Thomas J
authors: TJ
authors: Helton
authors: Anthony A
authors: AA
authors: Bavry
authors: Dharam J
authors: DJ
authors: Kumbhani
authors: Sandeep
authors: S
authors: Duggal
authors: Henri
authors: H
authors: Roukoz
authors: Deepak L
authors: DL
authors: Bhatt
mesh_terms: D001241:Aspirin / Q000009:adverse effects / Q000627:therapeutic use; D002318:Cardiovascular Diseases / Q000401:mortality / Q000517:prevention & control*; D000077144:Clopidogrel; D004359:Drug Therapy, Combination; D005260:Female; D006470:Hemorrhage / Q000139:chemically induced / Q000453:epidemiology; D006801:Humans; D008297:Male; D008875:Middle Aged; D009203:Myocardial Infarction / Q000517:prevention & control; D010975:Platelet Aggregation Inhibitors / Q000009:adverse effects / Q000627:therapeutic use*; D018570:Risk Assessment; D020521:Stroke / Q000517:prevention & control; D013988:Ticlopidine / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000627:therapeutic use
chemical_list: D010975:Platelet Aggregation Inhibitors; D000077144:Clopidogrel; D013988:Ticlopidine; D001241:Aspirin