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

• Published in: JACC. Cardiovascular interventions 2008-12, Vol.1 (6), p.631
• Main Authors: Aleil, Boris, Jacquemin, Laurent, De Poli, Fabien, Zaehringer, Michel, Collet, Jean-Philippe, Montalescot, Gilles, Cazenave, Jean-Pierre, Dickele, Marie-Claude, Monassier, Jean-Pierre, Gachet, Christian
• Format: Article
• Language: English
• Subjects: Aged; Angioplasty, Balloon, Coronary - adverse effects; Angioplasty, Balloon, Coronary - instrumentation; Aspirin - therapeutic use; Blood Platelets - drug effects; Blood Platelets - metabolism; Cell Adhesion Molecules - blood; 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
• ISSN: 1876-7605
• DOI: 10.1016/j.jcin.2008.09.004

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