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EXPEDITED PUBLICATION: LATE-BREAKING CLINICAL TRIAL

Adjusted Clopidogrel Loading Doses According to Vasodilator-Stimulated Phosphoprotein Phosphorylation Index Decrease Rate of Major Adverse Cardiovascular Events in Patients With Clopidogrel Resistance

A Multicenter Randomized Prospective Study

Laurent Bonello, MD^_*,_*, Laurence Camoin-Jau, MD, PhD, Stéphane Arques, MD, Christian Boyer, MD, Dimitri Panagides, MD, PhD^||, Olivier Wittenberg, MD^¶, Marie-Claude Simeoni, MD^#, Paul Barragan, MD^_**, Françoise Dignat-George, MD, PhD and Franck Paganelli, MD, PhD^_*

^_* Service de Cardiologie, Hôpital Universitaire Nord, Marseille, France
Laboratoire d’Hématologie, Unité INSERM UMRS 608, Hôpital de la Conception, Marseille, France
Service de Cardiologie, Hôpital d’Aubagne, Aubagne, France
Service de Cardiologie, Clinique Clairval, Marseille, France
^|| Service de Cardiologie, Clinique Bouchard, Marseille, France
^¶ Service de Cardiologie, Hôpital Privé Beauregard, Marseille, France
^# Laboratoire de Statistique, Faculté de la Timone, Marseille, France
^_** Service de Cardiologie, Polyclinique les Fleurs, Ollioules, France.

Manuscript received October 11, 2007; revised manuscript received November 28, 2007, accepted December 17, 2007.

^_* Reprint requests and correspondence: Dr. Laurent Bonello, Département de Cardiologie, Hôpital Universitaire Nord, Chemin des Bourrely, 13015, Marseille, France. (Email: laurentbonello{at}yahoo.fr).

Objectives: This study evaluates the clinical impact of adjusting the loading dose of clopidogrel according to vasodilator-stimulated phosphoprotein (VASP) index in patients with clopidogrel resistance undergoing percutaneous coronary intervention (PCI).

Background: Clopidogrel resistance plays a key role in ischemic recurrence after PCI. In vitro tests of clopidogrel resistance can accurately predict major adverse cardiac events after PCI.

Methods: In this prospective, randomized, multicenter study, clopidogrel resistance was defined as a VASP index of more than 50% after a 600-mg loading dose. Patients with clopidogrel resistance undergoing coronary stenting were randomized to a control group or to the VASP-guided group, in which patients received additional bolus clopidogrel to decrease the VASP index below 50%.

Results: A total of 162 patients were included. The control (n = 84) and VASP-guided groups (n = 78) had similar demographic, clinical, and biological characteristics. In the VASP-guided group, dose adjustment was efficient in 67 patients (86%) and VASP index was significantly decreased (from 69.3 ± 10 to 37.6 ± 13.8; p < 0.001). Eight major adverse cardiac events (5%) were recorded during the 1-month follow-up, with a significantly lower rate in the VASP-guided group compared with the control group (0% vs. 10%; p = 0.007). There was no difference in the rate of major and minor bleeding (5% vs. 4%; p = 1).

Conclusions: This is the first study to suggest that adjusting the clopidogrel loading dose according to platelet monitoring using the VASP index is safe and may significantly improve the clinical outcome after PCI in patients with clopidogrel resistance despite a first 600-mg loading dose.

Abbreviations and Acronyms   ADP = adenosine diphosphate   MACE = major adverse cardiac events   MFI = mean fluorescence intensity   NSTEMI = non–ST-segment elevation myocardial infarction   PCI = percutaneous coronary intervention   PGE1 = prostaglandin E1   TIMI = Thrombolysis In Myocardial Infarction   VASP = vasodilator-stimulated phosphoprotein

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