The Relation of Dosing to Clopidogrel Responsiveness and the Incidence of High Post-Treatment Platelet Aggregation in Patients Undergoing Coronary Stenting

J Am Coll Cardiol. 2005 May 3;45(9):1392-6. doi: 10.1016/j.jacc.2005.01.030.

Abstract

Objectives: 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.

Publication types

  • Clinical Trial
  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adenosine Diphosphate
  • Aged
  • Clopidogrel
  • Coronary Stenosis / therapy*
  • Dose-Response Relationship, Drug
  • Female
  • Humans
  • Incidence
  • Male
  • Middle Aged
  • Platelet Aggregation / drug effects*
  • Platelet Aggregation Inhibitors / administration & dosage*
  • Postoperative Complications / prevention & control
  • Stents*
  • Ticlopidine / administration & dosage*
  • Ticlopidine / analogs & derivatives*
  • Treatment Outcome

Substances

  • Platelet Aggregation Inhibitors
  • Adenosine Diphosphate
  • Clopidogrel
  • Ticlopidine