title: 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.
abstract: OBJECTIVE
  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).
authors.affiliation: Institut National de la Santé et de la Recherche Médicale U311, Etablissement Français du Sang-Alsace, Strasbourg, France.
authors.forename: Boris
authors.initials: B
authors.lastname: Aleil
authors.forename: Laurent
authors.initials: L
authors.lastname: Jacquemin
authors.forename: Fabien
authors.initials: F
authors.lastname: De Poli
authors.forename: Michel
authors.initials: M
authors.lastname: Zaehringer
authors.forename: Jean-Philippe
authors.initials: JP
authors.lastname: Collet
authors.forename: Gilles
authors.initials: G
authors.lastname: Montalescot
authors.forename: Jean-Pierre
authors.initials: JP
authors.lastname: Cazenave
authors.forename: Marie-Claude
authors.initials: MC
authors.lastname: Dickele
authors.forename: Jean-Pierre
authors.initials: JP
authors.lastname: Monassier
authors.forename: Christian
authors.initials: C
authors.lastname: Gachet
mesh_terms: D000368:Aged; D015906:Angioplasty, Balloon, Coronary / Q000009:adverse effects / Q000295:instrumentation; D001241:Aspirin / Q000627:therapeutic use; D001792:Blood Platelets / Q000187:drug effects* / Q000378:metabolism; D015815:Cell Adhesion Molecules / Q000097:blood*; D000077144:Clopidogrel; D003324:Coronary Artery Disease / Q000097:blood / Q000628:therapy*; D004305:Dose-Response Relationship, Drug; D004334:Drug Administration Schedule; D004351:Drug Resistance; D004359:Drug Therapy, Combination; D005060:Europe; D005260:Female; D006470:Hemorrhage / Q000139:chemically induced; D006801:Humans; D008297:Male; D008840:Microfilament Proteins / Q000097:blood*; D008875:Middle Aged; D016017:Odds Ratio; D010750:Phosphoproteins / Q000097:blood*; D010766:Phosphorylation; D010975:Platelet Aggregation Inhibitors / Q000008:administration & dosage* / Q000009:adverse effects; D018048:Receptors, Purinergic P2 / Q000097:blood / Q000187:drug effects*; D058925:Receptors, Purinergic P2Y12; D018570:Risk Assessment; D015607:Stents; D013988:Ticlopidine / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives*; D013997:Time Factors; D000098662:Vasodilator-Stimulated Phosphoprotein
chemical_list: D015815:Cell Adhesion Molecules; D008840:Microfilament Proteins; C548576:P2RY12 protein, human; D010750:Phosphoproteins; D010975:Platelet Aggregation Inhibitors; D018048:Receptors, Purinergic P2; D058925:Receptors, Purinergic P2Y12; D000098662:Vasodilator-Stimulated Phosphoprotein; D000077144:Clopidogrel; D013988:Ticlopidine; D001241:Aspirin