2014
DOI: 10.1016/j.thromres.2014.01.003
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Impact of CYP2C19 Polymorphism and Proton Pump Inhibitors on Platelet Reactivity to Clopidogrel and Clinical Outcomes Following Stent Implantation

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Cited by 44 publications
(40 citation statements)
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“…Clopidogrel is a prodrug that requires hepatic biotransformation and has to be converted to an active metabolite [12]. Others and we have reported that CYP2C19 is an important factor in this activation process and that the presence of CYP2C19 loss-of-function (LOF) alleles is associated with high residual platelet reactivity (RPR) and adverse clinical outcomes in patients with coronary heart disease (CHD), especially patients following ACS and PCI [13][14][15][16][17]. In short, we need to consider the two points under the concomitant use Thrombosis Research 135 (2015) 1081-1086 of clopidogrel and PPI; drug-drug interaction with clopidogrel and PPI, and CYP2C19 polymorphism, which both could affect the antiplatelet efficacy of clopidogrel.…”
Section: Introductionmentioning
confidence: 99%
See 1 more Smart Citation
“…Clopidogrel is a prodrug that requires hepatic biotransformation and has to be converted to an active metabolite [12]. Others and we have reported that CYP2C19 is an important factor in this activation process and that the presence of CYP2C19 loss-of-function (LOF) alleles is associated with high residual platelet reactivity (RPR) and adverse clinical outcomes in patients with coronary heart disease (CHD), especially patients following ACS and PCI [13][14][15][16][17]. In short, we need to consider the two points under the concomitant use Thrombosis Research 135 (2015) 1081-1086 of clopidogrel and PPI; drug-drug interaction with clopidogrel and PPI, and CYP2C19 polymorphism, which both could affect the antiplatelet efficacy of clopidogrel.…”
Section: Introductionmentioning
confidence: 99%
“…We previously reported that the concomitant use of rabeprazole during dual antiplatelet therapy with clopidogrel and aspirin is not associated with high RPR [16] because rabeprazole is mostly metabolized by non-enzymatic pathways, and shows the least potent inhibition of CYP2C19 in vitro [18]. For other PPI, especially omeprazole, which is a major substrate and mostly metabolized by CYP2C19, there is concern about concomitant use with clopidogrel, although this is controversial [6,11,19].…”
Section: Introductionmentioning
confidence: 99%
“…Previous evidence has suggested that CYP enzymes not only play an important role in vascular tone, but are also associated with a higher risk of cardiovascular disease (8,18,28,29,31). CYP2C19 is expressed in human endothelial cells and catalyzes the biosynthesis of vasoprotective EETs (2, 6).…”
Section: Discussionmentioning
confidence: 99%
“…To ensure genotyping quality, we included DNA samples as internal controls, blinded samples of a known genotype, and negative controls (water). CYP2C19*2 and *3 are considered to account for Ͼ99% of the variant alleles that generate the null-activity enzyme in the Japanese population (8,14,18,29,31). Therefore, the patients were classified according to the CYP2C19 genotype into EMs carrying homozygous CYP2C19 wild-type alleles (CYP2C19*1/*1), IMs carrying one LOF allele (CYP2C19*2 or *3), and PMs carrying two of these alleles.…”
Section: Coronary Microvascular Disorder (Cmvd)mentioning
confidence: 99%
“…The study protocol was in agreement with the guideline of the ethical committee of Kumamoto University (Institutional Review Board of Kumamoto University), and written informed consent was obtained from each patient or the family of the subject. Residual PR was measured using a light transmission aggregometer (aggregation units•min, AU•min; MCM HEMA TRACER 313; PAM12C, LMS Inc., Japan) [9], and reactive hyperemia index (RHI) using RH-PAT as an index of endothelial dysfunction (Endo-PAT2000, Itamar Medical, Caesarea, Israel, software version 3.0.4) was examined. Cardiovascular event (cardiovascular death, myocardial infarction (MI), stroke, unstable angina, revascularization, intraprocedural thrombotic event (IPTE) and heart failure) was assessed according to male or female.…”
mentioning
confidence: 99%