title: Impact ofCYP2C19Variants on Clinical Efficacy of Clopidogrel and 1-Year Clinical Outcomes in Coronary Heart Patients Undergoing Percutaneous Coronary Intervention.
abstract: The impact of pharmacogenetic variants of cytochrome P450 2C19 (CYP2C19) on clopidogrel-mediated effects on platelet inhibition, inflammatory response and endothelial function, as well as risk of major adverse cardiovascular events (MACE), in coronary heart patients undergoing percutaneous coronary intervention (PCI) was investigated. To this end, we assessed the residual platelet aggregation rate (RPA), maximal aggregation rate (MAR) and plasma levels of sCD40L, sP-selectin, MMP-9, sVCAM-1 and sE-selectin after 24 h of PCI in 559 patients treated with clopidogrel and followed up for 1 year for evidence of MACE.CYP2C19*2and*3variants were identified using a clopidogrel-sensitive gene detection kit. Our results showed higher RPA and MAR as well as increased sE-selectin, sCD40L, sP-selectin, MMP-9, and sVCAM-1 levels in CYP2C19 intermediate metabolizer (IM,CYP2C19*1/*2, or*1/*3), poor metabolizer (PM,CYP2C19*2/*2,*2/*3, or*3/*3) and combined IM+PM groups, relative to those in extensive metabolizers (EM,CYP2C19*1/*1). In total, 519 patients completed 1 year of follow-up, among which 69 (13.3%) experienced MACE. The risk of MACE in CYP2C19 IM+PM patients was 2.664 times higher than that in CYP2C19 EM patients (OR = 2.664 (1.397-5.193),P= 0.004). The data suggest thatCYP2C19*2and*3variants modulate the drug efficacy of clopidogrel in coronary heart patients undergoing PCI and further enhance the risk of MACE. Accordingly,CYP2C19pharmacogenetic profiling may be beneficial for coronary heart patients undergoing PCI to predict the efficacy of treatment with clopidogrel. We propose that IM and PM patients should benefit from treatment with higher clopidogrel doses to improve efficacy and reduce the incidence of MACE.
authors.affiliation: Department of Pharmacy, The Second Xiangya Hospital, Central South UniversityChangsha, China; Institute of Clinical Pharmacy, Central South UniversityChangsha, China; Department of Pharmacy, Provincial Clinical College of Fujian Medical University, Fujian Provincial HospitalFuzhou, China.
authors.forename: Hong
authors.initials: H
authors.lastname: Sun
authors.affiliation: Department of Pharmacy, Xiangya Hospital, Central South University Changsha, China.
authors.forename: Qiang
authors.initials: Q
authors.lastname: Qu
authors.affiliation: Department of Pharmacy, Provincial Clinical College of Fujian Medical University, Fujian Provincial Hospital Fuzhou, China.
authors.forename: Zhen-Fan
authors.initials: ZF
authors.lastname: Chen
authors.affiliation: Department of Pharmacy, The Second Xiangya Hospital, Central South UniversityChangsha, China; Institute of Clinical Pharmacy, Central South UniversityChangsha, China.
authors.forename: Sheng-Lan
authors.initials: SL
authors.lastname: Tan
authors.affiliation: Department of Pharmacy, Provincial Clinical College of Fujian Medical University, Fujian Provincial Hospital Fuzhou, China.
authors.forename: Hai-Jun
authors.initials: HJ
authors.lastname: Zhou
authors.affiliation: Department of Pharmacy, The Second Xiangya Hospital, Central South UniversityChangsha, China; Institute of Clinical Pharmacy, Central South UniversityChangsha, China.
authors.forename: Jian
authors.initials: J
authors.lastname: Qu
authors.affiliation: Hypertension Laboratory, Provincial Clinical College of Fujian Medical University, Fujian Provincial Cardiovascular Disease Institute, Fujian Provincial Hospital Fuzhou, China.
authors.forename: Hui
authors.initials: H
authors.lastname: Chen
keywords: CYP2C19; PCI; antiplatelet therapy; clopidogrel; metabolizers