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Title

Biological effect of increased maintenance dose of clopidogrel in cardiovascular outpatients and influence of the cytochrome P450 2C19*2 allele on clopidogrel responsiveness

Authors
Senouf, David
Published in Thrombosis Research. 2008, vol. 121, no. 4, p. 463-8
Abstract INTRODUCTION: The first aim of this study is to evaluate the biological effect of doubling the maintenance dose of clopidogrel in pre-defined clopidogrel "low responders", compared to the biological effect of the standard dose in "responders". The second aim is to test the influence of the CYP 2C19*2 allele on clopidogrel responsiveness. MATERIALS AND METHODS: The platelet reactivity index (PRI), based on the phosphorylation status of the vasodilatator phosphoprotein, was determined in 81 consecutive cardiovascular outpatients who had been taking clopidogrel 75 mg/day for at least 15 days (visit 1). Patients with PRI>or=50% ("low responders") were then given clopidogrel 150 mg/day. All the patients were again evaluated 15 days later (visit 2) and were genotyped for the CYP 2C19*2 allele. RESULTS: At visit 1, PRI values ranged from 12.6% to 80.4%. In "low responders" (n=45), the mean PRI fell from 62.0+/-6.7% to 49.4+/-11.3% (P<0.001) after 15 days of clopidogrel 150 mg/day, while no significant change was observed in the other patients ("responders"), who remained on the standard dose (mean PRI: 37.7+/-10.4% and 39.9+/-10.8%, P=0.22, in visit 1 and 2, respectively). The CYP 2C19*2 allele was not associated with clopidogrel responsiveness. CONCLUSIONS: Increasing the maintenance dose of clopidogrel from 75 to 150 mg/day for 15 days in "low responders" is associated with a relative 20%-increase in its biological effect, independently of the CYP2C19 genotype, but without reaching the levels observed in "responders". The CYP 2C19*2 allele is not associated with clopidogrel responsiveness in our population of cardiovascular outpatients.
Keywords AdultAgedAllelesAryl Hydrocarbon Hydroxylases/geneticsCardiovascular Diseases/bloodFemaleHumansMaleMiddle AgedMixed Function Oxygenases/geneticsOutpatientsPlatelet Aggregation Inhibitors/pharmacologyTiclopidine/analogs & derivatives
Identifiers
PMID: 17681590
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Structures
Research groups Geneva Platelet Group (13)
Biologie du myocarde (22)
L'athérosclérose et ses complications cliniques (591)
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(ISO format)
FONTANA, Pierre, SENOUF, David, MACH, François. Biological effect of increased maintenance dose of clopidogrel in cardiovascular outpatients and influence of the cytochrome P450 2C19*2 allele on clopidogrel responsiveness. In: Thrombosis Research, 2008, vol. 121, n° 4, p. 463-8. https://archive-ouverte.unige.ch/unige:832

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Deposited on : 2009-02-17

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