Clopidogrel 150 mg/day to Overcome Low Responsiveness in Patients Undergoing Elective Percutaneous Coronary Intervention: Results From the VASP-02 (Vasodilator-Stimulated Phosphoprotein-02) Randomized Study

JACC Cardiovasc Interv. 2008 Dec;1(6):631-8. doi: 10.1016/j.jcin.2008.09.004.

Abstract

Objectives: We investigated whether maintenance therapy with clopidogrel 150 mg/day produces greater platelet inhibition than the standard 75-mg/day dose and whether the higher maintenance dose increases platelet inhibition in low responders to clopidogrel 75 mg/day.

Background: Patients show interindividual variability in their platelet response to clopidogrel. Low responders could potentially obtain greater clinical benefit from greater doses of clopidogrel.

Methods: One hundred fifty-three elective percutaneous coronary intervention patients were randomized to clopidogrel 150 mg/day (n = 58) or 75 mg/day (n = 95) for 4 weeks, with vasodilator-stimulated phosphoprotein assay-guided switching to clopidogrel 150 mg/day after 2 weeks in low responders (platelet reactivity index >or=69%). All patients received aspirin 75 mg/day.

Results: After 2 weeks, clopidogrel 150 mg/day produced a significantly lower platelet reactivity index than clopidogrel 75 mg/day (43.9 +/- 17.3% vs. 58.6 +/- 17.7%; p < 0.0001). The proportion of low responders was significantly lower in patients randomized to clopidogrel 150 mg/day than in those randomized to clopidogrel 75 mg/day (8.6% vs. 33.7%; p = 0.0004). In the clopidogrel 75 mg/day group, 64.5% (20 of 31) of low responders became responders after switching to clopidogrel 150 mg/day for 2 weeks. No major bleeds occurred during the study; the incidence of minor bleeds was similar in each treatment group.

Conclusions: In elective percutaneous coronary intervention patients, a 150-mg/day clopidogrel maintenance dose produces greater inhibition of platelet function than clopidogrel 75 mg/day. In low responders to clopidogrel 75 mg/day, switching to clopidogrel 150 mg/day overcomes low responsiveness in a majority of patients. These findings warrant further clinical evaluation. (VASP-02; EudraCT number: 2004-005230-40).

Publication types

  • Comparative Study
  • Multicenter Study
  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Angioplasty, Balloon, Coronary* / adverse effects
  • Angioplasty, Balloon, Coronary* / instrumentation
  • Aspirin / therapeutic use
  • Blood Platelets / drug effects*
  • Blood Platelets / metabolism
  • Cell Adhesion Molecules / blood*
  • Clopidogrel
  • Coronary Artery Disease / blood
  • Coronary Artery Disease / therapy*
  • Dose-Response Relationship, Drug
  • Drug Administration Schedule
  • Drug Resistance*
  • Drug Therapy, Combination
  • Europe
  • Female
  • Hemorrhage / chemically induced
  • Humans
  • Male
  • Microfilament Proteins / blood*
  • Middle Aged
  • Odds Ratio
  • Phosphoproteins / blood*
  • Phosphorylation
  • Platelet Aggregation Inhibitors / administration & dosage*
  • Platelet Aggregation Inhibitors / adverse effects
  • Receptors, Purinergic P2 / blood
  • Receptors, Purinergic P2 / drug effects*
  • Receptors, Purinergic P2Y12
  • Risk Assessment
  • Stents
  • Ticlopidine / administration & dosage
  • Ticlopidine / adverse effects
  • Ticlopidine / analogs & derivatives*
  • Time Factors

Substances

  • Cell Adhesion Molecules
  • Microfilament Proteins
  • P2RY12 protein, human
  • Phosphoproteins
  • Platelet Aggregation Inhibitors
  • Receptors, Purinergic P2
  • Receptors, Purinergic P2Y12
  • vasodilator-stimulated phosphoprotein
  • Clopidogrel
  • Ticlopidine
  • Aspirin