Genetic and non-genetic factors responsible for antiplatelet effects of clopidogrel in Japanese patients undergoing coronary stent implantation: An algorithm to predict on-clopidogrel platelet reactivity |
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Authors: | Go Miura Noritaka Ariyoshi Yasunori Sato Hiroki Yamaguchi Yo Iwata Yoshihide Fujimoto Yoshio Kobayashi Itsuko Ishii |
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Affiliation: | 1. Department of Clinical Pharmacology, Graduate School of Pharmaceutical Sciences, Chiba University, Chiba, Japan;2. Division of Pharmacy, University Hospital, Chiba University School of Medicine, Chiba, Japan;3. Clinical Research Center, University Hospital, Chiba University School of Medicine, Chiba, Japan;4. Department of Cardiovascular Medicine, Chiba University Graduate School of Medicine, Chiba, Japan |
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Abstract: | IntroductionAntiplatelet effects of clopidogrel appear to be affected by various factors including genetic polymorphism. So far, there has been little information about the response of clopidogrel in Asians, whose prevalence of a CYP2C19 loss-of-function (LOF) allele is high.Methods and ResultsWe investigated background and clinical factors affecting on-clopidogrel platelet reactivity in Japanese patients undergoing coronary stent implantation (n = 114). In univariate analysis, antiplatelet effects of clopidogrel in a steady state were associated with not only CYP2C19 genotypes but also several factors including dyslipidemia. In addition, we developed an algorithm that can estimate P2Y12 Reaction Units (PRU) in a steady state by multiple regression analysis and evaluated the adequacy of the algorithm by the Akaike Information Criterion.ConclusionsWe revealed several factors influencing on-clopidogrel platelet reactivity in Japanese patients. We also succeeded in developing an algorithm that estimates PRU in a steady state, although it is uncertain whether the algorithm can be applied to other populations. |
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Keywords: | ACS, acute coronary syndromes AIC, Akaike Information Criterion BMI, body mass index BSA, body surface area CAG, coronary angiography CYP, cytochrome P450 DAPT, dual antiplatelet therapy DL, dyslipidemia DNA, deoxyribonucleic acid Hct, hematocrit HTPR, high on-clopidogrel treatment platelet reactivity LOF, loss of function PCI, percutaneous coronary intervention PLT, platelet count PON1, Paraoxonase-1 PPI, proton pump inhibitor PRU, P2Y12 Reaction Units RBC, red blood cell count WBC, white blood cell count |
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