Impact of CYP2C19 Polymorphism and Proton Pump Inhibitors on Platelet Reactivity to Clopidogrel and Clinical Outcomes Following Stent Implantation |
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Authors: | Seiji Hokimoto Michio Mizobe Tomonori Akasaka Yuichiro Arima Koichi Kaikita Kazuko Nakagawa Hisao Ogawa |
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Affiliation: | 1. Department of Cardiovascular Medicine, Graduate School of Medical Sciences, Kumamoto University, Kumamoto, Japan;2. Division of Pharmacology and Therapeutics, Graduate School of Medical and Pharmaceutical Sciences, Kumamoto University, Kumamoto, Japan |
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Abstract: | BackgroundThe response to clopidogrel, and some kind of the drug interaction are multifactorial.Methods and ResultsWe enrolled 174 consecutive patients and determined CYP2C19 genotypes, measured platelet aggregation, and assessed the relationship between CYP2C19 genotype and platelet reactivity 24 hours after clopidogrel administration, and the risk of cardiovascular events over 18 months follow-up. A sub analysis examined the impact of rabeprazole, a proton pump inhibitor (PPI) less affected by CYP2C19.The CYP2C19 genotype was extensive metabolizer (EM) in 36%, intermediate metabolizer (IM) in 45%, and poor metabolizer (PM) in 19%. Platelet reactivity was significantly lower in the EM group than in the IM and PM groups (EM, IM, PM: 3560 ± 1404, 4203 ± 1302, 5084 ± 1007 AU•min, P < 0.05). The cardiovascular event rate was higher in the IM and PM groups than in the EM group (12.7% and 12.5% vs 1.6%; Hazard ratio for IM 10.6, P = 0.029; for PM 11.3, P = 0.040). No differences were seen between patients taking (N = 50) and not taking (N = 124) rabeprazole in residual platelet aggregation (4407 ± 1360 vs 4048 ± 1394, AU•min, P = 0.2782), or in cardiovascular events (10.0% vs 8.1%, HR 0.97, P = 0.97).ConclusionsCYP2C19 genotype is associated with an increased risk of cardiovascular events following stent implantation in Japanese patients. |
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Keywords: | CYP2C19, Cytochrome P450 2C19 enzyme CHD, coronary heart disease FDA, Food and Drug Administration ACS, acute coronary syndrome PCIs, percutaneous coronary interventions PPIs, proton pump inhibitors ACCF, American College of Cardiology Foundation ACG, American College of Gastroenterology AHA, American Heart Association PCR, Polymerase chain reaction RFLPs, restriction fragment length polymorphisms EM, extensive metabolizers IM, intermediate metabolizers PM, poor metabolizers ADP, adenosine diphosphate |
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