title: Optimal timing for the initiation of pre-treatment with 300 mg clopidogrel before percutaneous coronary intervention.
abstract: OBJECTIVE
  This study sought to determine the optimal timing of a 300-mg clopidogrel loading dose before percutaneous coronary intervention (PCI) in patients enrolled in the Clopidogrel for the Reduction of Events During Observation (CREDO) trial.
  
  
  BACKGROUND
  A loading dose of clopidogrel before a PCI has become relatively commonplace, although the data supporting this practice are limited and sometimes conflicting.
  
  
  METHODS
  Patients were randomized to receive either 300 mg clopidogrel or a matching placebo administered a minimum of 3 h and a maximum of 24 h before PCI. The primary 28-day combined end point was death, myocardial infarction, or urgent target vessel revascularization. Linear splines were used to summarize the effect of the time of pre-treatment as a continuous variable.
  
  
  RESULTS
  A total of 1,762 patients were evaluated. For patients randomized to placebo, there was no relationship between the duration of pre-treatment and the occurrence of the primary end point, whereas longer durations of pre-treatment in patients randomized to clopidogrel were associated with improved outcomes. The event rates diverged maximally at 24 h. The difference in outcomes between placebo and clopidogrel pre-treated patients was not significant until > or =15 h pre-treatment, with a 58.8% (p = 0.028) reduction in the primary end point in patients pre-treated with clopidogrel > or =15 h compared with placebo.
  
  
  CONCLUSIONS
  When a 300-mg loading dose of clopidogrel is used, little benefit is obtained compared with just 75 mg at the time of the PCI when the treatment duration is <12 h. In patients pre-treated for longer durations, the optimal duration seems to approach 24 h.
authors.affiliation: Linda and Jack Gill Heart Institute, University of Kentucky, Lexington, Kentucky, USA. Steinhubl@uky.edu
authors.forename: Steven R
authors.initials: SR
authors.lastname: Steinhubl
authors.forename: Peter B
authors.initials: PB
authors.lastname: Berger
authors.forename: Danielle M
authors.initials: DM
authors.lastname: Brennan
authors.forename: Eric J
authors.initials: EJ
authors.lastname: Topol
mesh_terms: D015906:Angioplasty, Balloon, Coronary; D000077144:Clopidogrel; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D017202:Myocardial Ischemia / Q000517:prevention & control*; D010975:Platelet Aggregation Inhibitors / Q000008:administration & dosage*; D011183:Postoperative Complications / Q000453:epidemiology / Q000517:prevention & control*; D011300:Preoperative Care; D013988:Ticlopidine / Q000008:administration & dosage / Q000031:analogs & derivatives*; D013997:Time Factors
chemical_list: D010975:Platelet Aggregation Inhibitors; D000077144:Clopidogrel; D013988:Ticlopidine