High clopidogrel loading dose during coronary stenting: effects on drug response and interindividual variability

Eur Heart J. 2004 Nov;25(21):1903-10. doi: 10.1016/j.ehj.2004.07.036.

Abstract

Aim: To assess platelet inhibitory effects, interindividual variability in platelet inhibition as well as response to a 600 mg, compared to a standard 300 mg, clopidogrel loading dose (LD) after coronary stenting

Methods and results: Platelet function profiles were assessed in 50 patients undergoing coronary stenting receiving either a 300 mg (n=27) or 600 mg clopidogrel LD. ADP (6 microM) and collagen (6 microg/mL) induced platelet aggregation, as well as ADP (2 microM) induced glycoprotein (GP) IIb/IIIa activation and P-selectin expression were assessed at baseline and 4, 24, and 48 h following clopidogrel front-loading. A more intense and rapid inhibition of platelet activation (both GP IIb/IIIa activation and P-selectin expression) were achieved using a 600 mg, compared to a 300 mg, LD throughout the entire 48 hours (p<0.001). Although there were no differences in platelet aggregation, overall a 600 mg LD increased the number of clopidogrel responders and this was also achieved earlier compared to a 300 mg LD. A 600 mg LD did not reduce interindividual variability of platelet response.

Conclusion: The use of a 600 mg clopidogrel LD in patients undergoing coronary stenting optimises platelet inhibitory effects early after intervention and may provide a more effective protection against early thrombotic complications.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Blood Platelets / drug effects*
  • Blood Platelets / physiology
  • Clopidogrel
  • Coronary Artery Disease / surgery*
  • Female
  • Humans
  • Male
  • Middle Aged
  • P-Selectin / metabolism
  • Platelet Activation / drug effects
  • Platelet Aggregation Inhibitors / administration & dosage*
  • Platelet Membrane Glycoprotein IIb / metabolism
  • Risk Factors
  • Stents*
  • Ticlopidine / administration & dosage*
  • Ticlopidine / analogs & derivatives*

Substances

  • P-Selectin
  • Platelet Aggregation Inhibitors
  • Platelet Membrane Glycoprotein IIb
  • Clopidogrel
  • Ticlopidine