title: Dose comparisons of clopidogrel and aspirin in acute coronary syndromes.
abstract: BACKGROUND
  Clopidogrel and aspirin are widely used for patients with acute coronary syndromes and those undergoing percutaneous coronary intervention (PCI). However, evidence-based guidelines for dosing have not been established for either agent.
  
  
  METHODS
  We randomly assigned, in a 2-by-2 factorial design, 25,086 patients with an acute coronary syndrome who were referred for an invasive strategy to either double-dose clopidogrel (a 600-mg loading dose on day 1, followed by 150 mg daily for 6 days and 75 mg daily thereafter) or standard-dose clopidogrel (a 300-mg loading dose and 75 mg daily thereafter) and either higher-dose aspirin (300 to 325 mg daily) or lower-dose aspirin (75 to 100 mg daily). The primary outcome was cardiovascular death, myocardial infarction, or stroke at 30 days.
  
  
  RESULTS
  The primary outcome occurred in 4.2% of patients assigned to double-dose clopidogrel as compared with 4.4% assigned to standard-dose clopidogrel (hazard ratio, 0.94; 95% confidence interval [CI], 0.83 to 1.06; P=0.30). Major bleeding occurred in 2.5% of patients in the double-dose group and in 2.0% in the standard-dose group (hazard ratio, 1.24; 95% CI, 1.05 to 1.46; P=0.01). Double-dose clopidogrel was associated with a significant reduction in the secondary outcome of stent thrombosis among the 17,263 patients who underwent PCI (1.6% vs. 2.3%; hazard ratio, 0.68; 95% CI, 0.55 to 0.85; P=0.001). There was no significant difference between higher-dose and lower-dose aspirin with respect to the primary outcome (4.2% vs. 4.4%; hazard ratio, 0.97; 95% CI, 0.86 to 1.09; P=0.61) or major bleeding (2.3% vs. 2.3%; hazard ratio, 0.99; 95% CI, 0.84 to 1.17; P=0.90).
  
  
  CONCLUSIONS
  In patients with an acute coronary syndrome who were referred for an invasive strategy, there was no significant difference between a 7-day, double-dose clopidogrel regimen and the standard-dose regimen, or between higher-dose aspirin and lower-dose aspirin, with respect to the primary outcome of cardiovascular death, myocardial infarction, or stroke. (Funded by Sanofi-Aventis and Bristol-Myers Squibb; ClinicalTrials.gov number, NCT00335452.)
authors.forename: Shamir R
authors.initials: SR
authors.lastname: Mehta
authors.forename: Jean-Pierre
authors.initials: JP
authors.lastname: Bassand
authors.forename: Susan
authors.initials: S
authors.lastname: Chrolavicius
authors.forename: Rafael
authors.initials: R
authors.lastname: Diaz
authors.forename: John W
authors.initials: JW
authors.lastname: Eikelboom
authors.forename: Keith A A
authors.initials: KA
authors.lastname: Fox
authors.forename: Christopher B
authors.initials: CB
authors.lastname: Granger
authors.forename: Sanjit
authors.initials: S
authors.lastname: Jolly
authors.forename: Campbell D
authors.initials: CD
authors.lastname: Joyner
authors.forename: Hans-Jurgen
authors.initials: HJ
authors.lastname: Rupprecht
authors.forename: Petr
authors.initials: P
authors.lastname: Widimsky
authors.forename: Rizwan
authors.initials: R
authors.lastname: Afzal
authors.forename: Janice
authors.initials: J
authors.lastname: Pogue
authors.forename: Salim
authors.initials: S
authors.lastname: Yusuf
mesh_terms: D054058:Acute Coronary Syndrome / Q000188:drug therapy* / Q000401:mortality / Q000628:therapy; D000368:Aged; D015906:Angioplasty, Balloon, Coronary; D001241:Aspirin / Q000008:administration & dosage* / Q000009:adverse effects; D002318:Cardiovascular Diseases / Q000401:mortality / Q000517:prevention & control; D000077144:Clopidogrel; D003131:Combined Modality Therapy; D017023:Coronary Angiography; D001026:Coronary Artery Bypass; D004311:Double-Blind Method; D005260:Female; D006470:Hemorrhage / Q000139:chemically induced / Q000401:mortality; D006801:Humans; D053208:Kaplan-Meier Estimate; D008297:Male; D008875:Middle Aged; D009203:Myocardial Infarction / Q000453:epidemiology; D010975:Platelet Aggregation Inhibitors / Q000008:administration & dosage* / Q000009:adverse effects; D012107:Research Design; D020521:Stroke / Q000453:epidemiology; D013988:Ticlopidine / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives*
chemical_list: D010975:Platelet Aggregation Inhibitors; D000077144:Clopidogrel; D013988:Ticlopidine; D001241:Aspirin