This Article Figures Only Full Text Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Services Email this article to a friend Similar articles in this journal Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Aleil, B. Articles by Gachet, C. Search for Related Content PubMed Articles by Aleil, B. Articles by Gachet, C.

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

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, Christian Gachet, MD, PhD^_*,_*

^_* Institut National de la Santé et de la Recherche Médicale U.311, Etablissement Français du Sang-Alsace, Strasbourg, France
Service de Cardiologie, Clinique de l'Orangerie, Strasbourg, France
Service de Cardiologie, Hôpital Emile Muller, Mulhouse
Service de Cardiologie, Centre Hospitalier Général, Haguenau, France
^|| Institut de Cardiologie and INSERM U856, Hôpital Pitié-Salpêtrière (AP-HP), Paris, France

^_* Reprint requests and correspondence: Dr. Christian Gachet, EFS-Alsace, 10, rue Spielmann, B.P. No. 36, F-67065 Strasbourg. Cedex, France (Email: christian.gachet{at}efs-alsace.fr).

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).

Key Words: clopidogrel • coronary stenting • platelet function

Abbreviations and Acronyms   ADP = adenosine diphosphate   CI = confidence interval   MFI = mean fluorescence intensity   OR = odds ratio   PCI = percutaneous coronary intervention   PGE1 = prostaglandin E1   PPI = proton-pump inhibitor   PRI = platelet reactivity index   VASP = vasodilator-stimulated phosphoprotein

This article has been cited by other articles:

				How Should Clopidogrel Nonresponders Be Treated? Journal Watch Cardiology, January 21, 2009; 2009(121): 2 - 2. [Full Text]

				S. B. King III and K. M. Momary Thienopyridines: Time for Personalized Therapy? J. Am. Coll. Cardiol. Intv., December 1, 2008; 1(6): 718 - 719. [Full Text] [PDF]