IMPACT OF CYTOCHROME P450 3A5 POLYMORPHISM ON PLATELET AGGREGATION ON MAINTENANCE TREATMENT WITH CLOPIDOGREL IN PATIENTS UNDERGOING ELECTIVE CORONARY STENTING

Abstract

Background: High residual platelet reactivity in patients receiving clopidogrel may be associated with an increased risk of stent thrombosis after coronary stenting. The aim was to evaluate the impact of CYP3A5 polymorphism, as well as CYP2C19, on platelet reactivity during dual antiplatelet therapy. Methods: We examined CYP2C19, and CYP3A5 genotypes, and measured the platelet aggregation induced by adenosine diphosphate using light transmittance aggregometry at early and late phase (clopidogrel loading dose 300mg, maintenance dose 75mg) in 62 patients (male 39, age 67yrs) treated with stenting on dual antiplatelet agent. Results: The distribution of CYP2C19 genotype was 31, 42, and 27 % in the extensive metabolizer (EM;CYP2C19*1/*1), in the intermediate metabolizer (IM;*1/*2, *1/*3), and in the poor metabolizer (PM;*2/*2, *2/*3, *3/*3), respectively. The values of platelet reactivity at early phase were 4069+/-1383, 4407+/-1755, and 5301+/-807 AU*min in the EM, in the IM and in the PM, respectively. The values of platelet reactivity at late phase were 2948+/-1427, 3068+/-1656, and 4465+/-1557 AU*min in the EM, in the IM and in the PM, respectively. (P<0.05) The distribution of CYP3A5 genotype was 32 and 68 %, in patients carrying wild-type or one loss-of-function allele (Expressor; *1/ *1, *1 / *3), and in the *3 homozygotes carrying two loss-of-function alleles (non-Expressor; *3 / *3), respectively. In the patients with CYP2C19 PM, platelet reactivities according to CYP3A5 genotype at late phase were 3398+/-1143, and 5175+/-1415 AU*min, in Expressor, and in non-Expressor, respectively. (P<0.01) Conclusions: These data suggest that antiplatelet response to clopidogrel at late phase might depend on CYP3A5 polymorphism in patients with CYP2C19 PM.