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

Thrombosis Journal

Original Clinical Investigation

Alf-Aage R Pettersen¹  Trine B Opstad¹  Harald Arnesen²  Ingebjorg Seljeflot² 

[1] Center for Clinical Heart Research. Department of Cardiology, Oslo University Hospital, Ullevaal, Oslo, Norway;Center for Clinical Heart Research. Department of Cardiology, Oslo University Hospital, Ullevaal, Oslo, Norway;Faculty of Medicine, University of Oslo, Oslo, Norway;

关键词: Clopidogrel resistance;    Functional tests;    VerifyNow method;    VASP method;    Genetic polymorphisms;   

DOI  :  10.1186/1477-9560-9-4

 received in 2011-01-10, accepted in 2011-03-22,  发布年份 2011

来源: Springer

【 摘 要 】

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 RegistrationClinicalTrials.gov: NCT00222261

【 授权许可】

CC BY   
© Pettersen et al; licensee BioMed Central Ltd. 2011