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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

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