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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
Authors:Go Miura  Noritaka Ariyoshi  Yasunori Sato  Hiroki Yamaguchi  Yo Iwata  Yoshihide Fujimoto  Yoshio Kobayashi  Itsuko Ishii
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
Abstract:

Introduction

Antiplatelet 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 Results

We 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.

Conclusions

We 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.
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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