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.
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).
Aleil
Boris
B
Institut National de la Santé et de la Recherche Médicale U311, Etablissement Français du Sang-Alsace, Strasbourg, France.
Jacquemin
Laurent
L
De Poli
Fabien
F
Zaehringer
Michel
M
Collet
Jean-Philippe
JP
Montalescot
Gilles
G
Cazenave
Jean-Pierre
JP
Dickele
Marie-Claude
MC
Monassier
Jean-Pierre
JP
Gachet
Christian
C
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
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