The influence of CYP 2C19*2 polymorphism on platelet function testing during single antiplatelet treatment with clopidogrelReport as inadecuate

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Thrombosis Journal

, 9:4

First Online: 22 March 2011Received: 10 January 2011Accepted: 22 March 2011


BackgroundDifferent platelet function tests can be used to evaluate the degree of achieved platelet inhibition in patients treated with clopidogrel. The presence of CYP 2C19*2 polymorphism can reduce the formation of the active metabolite of clopidogrel, resulting in less platelet inhibition.

Patients and MethodsPatients with symptomatic coronary artery disease, all on chronic single aspirin treatment were randomized to continue on aspirin or change to clopidogrel. In 219 randomly selected clopidogrel treated patients, platelet reactivity was evaluated by VASP-PRI determination and by use of VerifyNow P2Y12-PRU. The CYP 2C19*2 G-A polymorphism was further determined.

ResultsThe total frequency of clopidogrel resistance was 29.0% by VASP-PRI and 31.6% by VerifyNow-PRU. The number of patients being hetero- and homozygous combined for the CYP 2C19*2 polymorphism GA-AA was 64 29%. Platelet reactivity was significantly higher in patients with the polymorphism compared to wild-type patients GG. VASP-PRI was 50.9% SD19 in patients having the polymorphism compared to 38.3% SD21 in patients with the GG genotype p = 0.001. Correspondingly, the mean PRU was 165 SD67 compared to 124 SD69 p < 0.001. The frequency of clopidogrel resistance in patients with the polymorphism was 32% compared to 16% in wild-type patients when defined by VASP-PRI p = 0.006. When defined by PRU VerifyNow, the corresponding frequencies were 53% and 22% p < 0.001.

ConclusionsClopidogrel treated patients with the CYP 2C19*2 polymorphism have significantly increased platelet reactivity compared to patients with the wild-type, evaluated with the VASP determination, and even more pronounced with the VerifyNow P2Y12 method.

Trial NCT00222261

KeywordsClopidogrel resistance Functional tests VerifyNow method VASP method Genetic polymorphisms Electronic supplementary materialThe online version of this article doi:10.1186-1477-9560-9-4 contains supplementary material, which is available to authorized users.

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Author: Alf-Aage R Pettersen - Harald Arnesen - Trine B Opstad - Ingebjorg Seljeflot


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