title: Early and sustained dual oral antiplatelet therapy following percutaneous coronary intervention: a randomized controlled trial.
abstract: BACKGROUND
  Following percutaneous coronary intervention (PCI), short-term clopidogrel therapy in addition to aspirin leads to greater protection from thrombotic complications than aspirin alone. However, the optimal duration of combination oral antiplatelet therapy is unknown. Also, although current clinical data suggest a benefit for beginning therapy with a clopidogrel loading dose prior to PCI, the practical application of this therapy has not been prospectively studied.
  
  
  OBJECTIVE
  To evaluate the benefit of long-term (12-month) treatment with clopidogrel after PCI and to determine the benefit of initiating clopidogrel with a preprocedure loading dose, both in addition to aspirin therapy.
  
  
  METHODS
  The Clopidogrel for the Reduction of Events During Observation (CREDO) trial, a randomized, double-blind, placebo-controlled trial conducted among 2116 patients who were to undergo elective PCI or were deemed at high likelihood of undergoing PCI, enrolled at 99 centers in North America from June 1999 through April 2001.
  
  
  METHODS
  Patients were randomly assigned to receive a 300-mg clopidogrel loading dose (n = 1053) or placebo (n = 1063) 3 to 24 hours before PCI. Thereafter, all patients received clopidogrel, 75 mg/d, through day 28. From day 29 through 12 months, patients in the loading-dose group received clopidogrel, 75 mg/d, and those in the control group received placebo. Both groups received aspirin throughout the study.
  
  
  METHODS
  One-year incidence of the composite of death, myocardial infarction (MI), or stroke in the intent-to-treat population; 28-day incidence of the composite of death, MI, or urgent target vessel revascularization in the per-protocol population.
  
  
  RESULTS
  At 1 year, long-term clopidogrel therapy was associated with a 26.9% relative reduction in the combined risk of death, MI, or stroke (95% confidence interval [CI], 3.9%-44.4%; P =.02; absolute reduction, 3%). Clopidogrel pretreatment did not significantly reduce the combined risk of death, MI, or urgent target vessel revascularization at 28 days (reduction, 18.5%; 95% CI, -14.2% to 41.8%; P =.23). However, in a prespecified subgroup analysis, patients who received clopidogrel at least 6 hours before PCI experienced a relative risk reduction of 38.6% (95% CI, -1.6% to 62.9%; P =.051) for this end point compared with no reduction with treatment less than 6 hours before PCI. Risk of major bleeding at 1 year increased, but not significantly (8.8% with clopidogrel vs 6.7% with placebo; P =.07).
  
  
  CONCLUSIONS
  Following PCI, long-term (1-year) clopidogrel therapy significantly reduced the risk of adverse ischemic events. A loading dose of clopidogrel given at least 3 hours before the procedure did not reduce events at 28 days, but subgroup analyses suggest that longer intervals between the loading dose and PCI may reduce events.
authors.affiliation: Division of Cardiology, University of North Carolina, CB#7075, 338 Burnett-Womack Bldg, Chapel Hill, NC 27599, USA. steven_steinhubl@med.unc.edu
authors.forename: Steven R
authors.initials: SR
authors.lastname: Steinhubl
authors.forename: Peter B
authors.initials: PB
authors.lastname: Berger
authors.forename: J Tift
authors.initials: JT
authors.lastname: Mann
authors.forename: Edward T A
authors.initials: ET
authors.lastname: Fry
authors.forename: Augustin
authors.initials: A
authors.lastname: DeLago
authors.forename: Charles
authors.initials: C
authors.lastname: Wilmer
authors.forename: Eric J
authors.initials: EJ
authors.lastname: Topol
mesh_terms: D000284:Administration, Oral; D000368:Aged; D015906:Angioplasty, Balloon, Coronary; D001241:Aspirin / Q000008:administration & dosage / Q000627:therapeutic use*; D000077144:Clopidogrel; D004311:Double-Blind Method; D004334:Drug Administration Schedule; D004359:Drug Therapy, Combination; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D009203:Myocardial Infarction / Q000517:prevention & control; D010975:Platelet Aggregation Inhibitors / Q000008:administration & dosage / Q000627:therapeutic use*; D020521:Stroke / Q000517:prevention & control; D016019:Survival Analysis; D013927:Thrombosis / Q000517:prevention & control*; D013988:Ticlopidine / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000627:therapeutic use*; D016896:Treatment Outcome
chemical_list: D010975:Platelet Aggregation Inhibitors; D000077144:Clopidogrel; D013988:Ticlopidine; D001241:Aspirin