Intra-individual variability in clopidogrel responsiveness in coronary artery disease patients under long term therapy

Platelets. 2010;21(7):503-7. doi: 10.3109/09537104.2010.499483.

Abstract

Clopidogrel responsiveness (CR) following a loading dose (LD) predicts thrombotic events after percutaneous coronary interventions (PCI). Some of the mechanisms involved in large inter-individual variability in CR may be varied. We therefore postulated that there may be an intra-individual variability in CR. Two hundred and one patients receiving long-term therapy with aspirin and clopidogrel after drug-eluting stents PCI were prospectively included in this monocentre study along with any patient re-admitted within 12 months post-PCI. Platelet reactivity (PR) inhibition was assessed by the vasodilator phosphoprotein (VASP) index following a 600 mg loading dose of clopidogrel on each admission to determine CR (VASP 1 during the first admission and VASP 2 during re-admission). DeltaVASP = VASP 2 –VASP 1 was used to study intra-individual variability in CR. We observed that the response to a 600 mg LD of clopidogrel was poorly correlated within an individual (kappa = 0.33; p < 0.001 (n = 201)). Although most patients had increased platelet inhibition at the time of readmission, 35.3% of patients exhibited a decreased platelet inhibition despite chronic clopidogrel therapy and a 600 mg reload. Quartiles analysis of DeltaVASP demonstrated that insulin-treated diabetes was associated with decreased CR over time (p = 0.03). In addition to the large inter-individual variability in clopidogrel responsiveness, there is large intra-individual variability. Decreased clopidogrel responsiveness despite long-term clopidogrel therapy could be a trigger for recurrent thrombotic events.

Publication types

  • Clinical Trial

MeSH terms

  • Aspirin / administration & dosage
  • Blood Platelets / drug effects
  • Cell Adhesion Molecules / blood
  • Clopidogrel
  • Coronary Artery Disease / blood
  • Coronary Artery Disease / drug therapy*
  • Drug-Eluting Stents
  • Female
  • Humans
  • Individuality
  • Male
  • Microfilament Proteins / blood
  • Middle Aged
  • Phosphoproteins / blood
  • Platelet Aggregation Inhibitors / administration & dosage*
  • Prospective Studies
  • Ticlopidine / administration & dosage
  • Ticlopidine / analogs & derivatives*

Substances

  • Cell Adhesion Molecules
  • Microfilament Proteins
  • Phosphoproteins
  • Platelet Aggregation Inhibitors
  • vasodilator-stimulated phosphoprotein
  • Clopidogrel
  • Ticlopidine
  • Aspirin