title: The relation of dosing to clopidogrel responsiveness and the incidence of high post-treatment platelet aggregation in patients undergoing coronary stenting.
abstract: OBJECTIVE
  We determined the effect of clopidogrel dosing on the incidence of nonresponsiveness (NR) and high post-treatment platelet aggregation (post-PA).
  
  
  BACKGROUND
  We have reported NR after a 300-mg loading dose. Limited information is available on the comparative effect of a 600-mg loading dose on the incidence of NR and high post-PA.
  
  
  METHODS
  Clopidogrel responsiveness and post-PA were measured in patients undergoing stenting (n = 190) randomly treated with either a 300-mg or a 600-mg clopidogrel load. Nonresponsiveness was defined as <10% absolute change in platelet aggregation, and high post-PA was defined as >75th percentile aggregation after 300 mg clopidogrel.
  
  
  RESULTS
  Nonresponsiveness was lower after 600 mg compared to the 300-mg dose (8% vs. 28% and 8% vs. 32% with 5 and 20 microM ADP, respectively, p < 0.001). Among the patients with high post-PA after 300 mg clopidogrel, 62% to 65% had NR, whereas after the 600-mg dose, all of the patients with high post-PA had NR.
  
  
  CONCLUSIONS
  A 600-mg clopidogrel loading dose reduces the incidence of NR and high post-PA as compared to a 300-mg dose. Higher dosing strategies and methods to confirm platelet inhibition should be further investigated in order to optimally use clopidogrel in patients undergoing stenting.
authors.affiliation: Sinai Center for Thrombosis Research, Baltimore, Maryland 21215, USA. pgurbel@lifebridgehealth.org
authors.forename: Paul A
authors.initials: PA
authors.lastname: Gurbel
authors.forename: Kevin P
authors.initials: KP
authors.lastname: Bliden
authors.forename: Kevin M
authors.initials: KM
authors.lastname: Hayes
authors.forename: Jason A
authors.initials: JA
authors.lastname: Yoho
authors.forename: William R
authors.initials: WR
authors.lastname: Herzog
authors.forename: Udaya S
authors.initials: US
authors.lastname: Tantry
mesh_terms: D000244:Adenosine Diphosphate; D000368:Aged; D000077144:Clopidogrel; D023921:Coronary Stenosis / Q000628:therapy*; D004305:Dose-Response Relationship, Drug; D005260:Female; D006801:Humans; D015994:Incidence; D008297:Male; D008875:Middle Aged; D010974:Platelet Aggregation / Q000187:drug effects*; D010975:Platelet Aggregation Inhibitors / Q000008:administration & dosage*; D011183:Postoperative Complications / Q000517:prevention & control; D015607:Stents; D013988:Ticlopidine / Q000008:administration & dosage* / Q000031:analogs & derivatives*; D016896:Treatment Outcome
chemical_list: D010975:Platelet Aggregation Inhibitors; D000244:Adenosine Diphosphate; D000077144:Clopidogrel; D013988:Ticlopidine