Abstract
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
Highlights
Different platelet function tests can be used to evaluate the degree of achieved platelet inhibition in patients treated with clopidogrel
Platelet reactivity was significantly higher in patients with the polymorphism compared to wild-type patients (GG)
Clopidogrel 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
Summary
Different 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. Despite improvement in antiplatelet regimens, patients on-treatment run a considerable risk for new thrombotic events [4]. Clinical benefit has been shown with clopidogrel, interindividual variation of platelet inhibition has been focused as an important explanation of insufficient platelet inhibition that might be a risk factor for new thrombotic events. Clopidogrel is metabolized to the active metabolite that inhibits the ADP receptor P2Y12, and thereby inhibiting the ADP mediated platelet activation. This metabolization is dependent on the hepatic cytochrome P450 isoenzymes like CYP2C19, CYP1A2, CYP2B6, CYP2C9 and CYP3A4. Clopidogrel response variability is, to a large extent, explained by the extent of formation of the active metabolite of the drug [8]
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