Author + information
- Received August 6, 2008
- Accepted September 2, 2008
- Published online December 1, 2008.
- Boris Aleil, MD, PhD⁎,†,
- Laurent Jacquemin, MD‡,
- Fabien De Poli, MD§,
- Michel Zaehringer, MD†,
- Jean-Philippe Collet, MD PhD∥,
- Gilles Montalescot, MD, PhD∥,
- Jean-Pierre Cazenave, MD, PhD⁎,
- Marie-Claude Dickele, MD§,
- Jean-Pierre Monassier, MD, FESC‡ and
- Christian Gachet, MD, PhD⁎,⁎ ()
- ↵⁎Reprint requests and correspondence:
Dr. Christian Gachet, EFS-Alsace, 10, rue Spielmann, B.P. No. 36, F-67065 Strasbourg. Cedex, France
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 ≥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).
This work was sponsored and supported by Association de Recherche et de Développement en Médecine et Santé Publique (ARMESA), Etablissement Français du Sang (EFS)-Alsace with a research grant from Sanofi-Aventis and Bristol-Myers Squibb.
- Received August 6, 2008.
- Accepted September 2, 2008.
- American College of Cardiology Foundation