Correlation Between the <i>CYP2C19</i> Phenotype Status and the Results of Three Different Platelet Function Tests in Cardiovascular Disease Patients Receiving Antiplatelet Therapy: An Emphasis on Newly Introduced Platelet Function Analyzer-200 P2Y Test

Li, Shuhua; Choi, Jaehyuk; Guo, Long; Goh, Ri Young; Kim, Bo Ram; Woo, Kwang‐Sook; Kim, Moo Hyun; Han, Jin Yeong

doi:10.3343/alm.2016.36.1.42

Cited by 16 publications

(16 citation statements)

References 24 publications

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“…An increasing number of studies conducted in Asian countries show that reduced function CYP2C19 alleles are associated with an increased risk of vascular events . A recent study by Li et al reported loss‐of‐function CYP2C1P genotype in 59% of Korean patients with cardiovascular disease .…”

Section: Ethnic Distribution Of Cyp2c19 Polymorphisms—is It Clinicallmentioning

confidence: 99%

“…An increasing number of studies conducted in Asian countries show that reduced function CYP2C19 alleles are associated with an increased risk of vascular events. [60][61][62][63] A recent study by Li et al reported loss-of-function CYP2C1P genotype in 59% of Korean patients with cardiovascular disease. 63 Recent data corroborate that patients with CYP2C19 loss-of-function allele CYP2C19*2 are at increased risk for subsequent CVD events.…”

Section: Introductionmentioning

confidence: 99%

“…[60][61][62][63] A recent study by Li et al reported loss-of-function CYP2C1P genotype in 59% of Korean patients with cardiovascular disease. 63 Recent data corroborate that patients with CYP2C19 loss-of-function allele CYP2C19*2 are at increased risk for subsequent CVD events. For example, in a cohort of Japanese patients with ACS, 62.8% were found to have the PM phenotype as compared with 22.5% in a healthy Japanese cohort.…”

Section: Introductionmentioning

confidence: 99%

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East Asian perspective on the interaction between proton pump inhibitors and clopidogrel

Zou

Goh

2017

J of Gastro and Hepatol

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Both proton pump inhibitors (PPIs) and clopidogrel are widely prescribed in the Asia-Pacific population. PPIs are the mainstay therapeutic agents for prophylaxis against aspirin gastropathy and for acid-related disorders including gastroesophageal reflux disease. They are also co-prescribed with oral anticoagulant agents and with dual-antiplatelet therapy for the treatment and prevention of gastrointestinal bleeding. Clopidogrel belongs to the drug class of thienopyridines and is currently the most widely prescribed oral anticoagulant agent either alone or in combination with aspirin. Platelet inhibition by clopidogrel is prone to significant inter-individual variability and is believed to be affected by several factors such as genetics and drug-drug interactions. Since it was first reported in 2009, the potential for drug-drug interactions between PPIs and clopidogrel has remained headline news, and its significance in clinical practice is the subject of an ongoing debate. For East Asian patients in particular, the clinical relevance of the interaction between PPIs and clopidogrel remains unclear because of conflicting data, as well as underrepresentation of East Asian subjects in landmark trials. Increased CYP2C19 genetic polymorphisms in individuals from Asia-Pacific countries only fuel the confusion. Recent studies in East Asian cohorts suggests that the potential of PPIs to attenuate the efficacy of clopidogrel could be minimized by the use of newer PPIs with weaker affinity for the CYP2C19 isoenzyme, namely, pantoprazole, dexlansoprazole, and rabeprazole. This review aims to help clinicians choose the most appropriate PPI for co-prescription with clopidogrel in patients from Asia-Pacific countries.

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Section: Ethnic Distribution Of Cyp2c19 Polymorphisms—is It Clinicallmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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East Asian perspective on the interaction between proton pump inhibitors and clopidogrel

Zou

Goh

2017

J of Gastro and Hepatol

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“…Also the test was able to identify some non-responders to clopidogrel, identified initially using other approaches, in some groups of volunteers and patients of treated with this drug [71,72]. A further report indicated its usefulness in identifying patients with congenital defective responses to ADP [73] and there is also a correlation with CYP450 genotypes in clopidogrel-treated patients [74,75]. The sensitivity of the test is markedly influenced by the nature of the anticoagulant used in obtaining the blood for analysis [70] and it is likely that this should be taken account of in any future studies.…”

Section: Other Approaches To Assessing Platelet Reactivitymentioning

confidence: 83%

Novel Strategies for Assessing Platelet Reactivity

Algahtani

Heptinstall

2016

Future Cardiol.

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There are many approaches to assessing platelet reactivity and many uses for such measurements. Initially, measurements were based on the ability of platelets separated from other blood cells to aggregate together following activation with an appropriate 'aggregating agent'. Later, measurements of platelet aggregation in blood itself were performed, and this led to a point-of-care approach to platelet function testing. Measurement of secretory activity through the appearance of the activation marker Pselectin on platelets now provides an alternative approach, which enables remote testing. Measurement of vasodilator-stimulated phosphoprotein phosphorylation is also moving toward application in situations remote from the testing laboratory. Here we provide an overview of the various approaches that are now available, assess their advantages and disadvantages, and describe some of the clinical situations in which they are being used. Keywordsaspirin, flow cytometry, light transmission aggregometry (LTA), multiplate electrode aggregometry (MEA), P-selectin, P2Y12 antagonists, platelet aggregation, platelet reactivity, VASP phosphorylation, VerifyNow Platelet reactivity is a broad term indicating the degree of the response of blood platelets to an external stimulus, usually an 'aggregating agent'. Platelet reactivity can be measured in many different ways and the purpose of this review is to summarize the approaches, with an emphasis on the newer approaches that are becoming available.Platelets play an important role in the hemostatic process [1,2]. They contribute to the formation of a hemostatic plug that serves to prevent blood loss from injured blood vessels. The hemostatic plug contains thousands of platelets that have aggregated together within a network of fibrin. However, platelets also contribute to the generation of a thrombotic mass in a coronary or cerebral artery or in an artificial stent leading to blockage and resulting in conditions such as heart attack, stroke and stent thrombosis [3,4]. A thrombus is also composed of platelet aggregates within a fibrin network. So thrombus formation can thus be considered to be hemostasis in the wrong place.

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“…However, it is also reported that the genetic polymorphisms of its metabolizing enzyme, cytochrome P450 (CYP) 2C19, are involved in the antiplatelet effect of clopidogrel [4,5]. The CYP2C19 genotypes are classified based on rate of drug-metabolizing activity into three groups: extensive metabolizers (EM), intermediate metabolizers (IM), and poor metabolizers (PM), causing inter-individual variability in response to clopidogrel [6,7]. In addition, prevalence of IM and PM in the Japanese population is higher than in Western populations [6,8].…”

Section: Introductionmentioning

confidence: 99%

Prasugrel effectively reduces the platelet reactivity units in patients with genetically metabolic dysfunction of cytochrome P450 2C19 who are treated with long-term dual antiplatelet therapy after undergoing drug-eluting stent implantation

Shimamatsu

Sasaki

Katsuki³

et al. 2019

Heart Vessels

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Dual antiplatelet therapy (DAPT) with aspirin and P2Y 12 inhibitor is administered following percutaneous coronary intervention (PCI) with coronary stent implantation. Several studies have reported the effects of switching between P2Y 12 inhibitors on platelet reactivity (P2Y 12 reaction units: PRU), from acute to late phase after PCI. However, the effect of switching at very late phase is unknown. This study examined the effect on PRU in Japanese coronary heart disease patients with long-term DAPT (aspirin + clopidogrel) when switching from clopidogrel to prasugrel. Ninety-six patients were enrolled in this study. The median DAPT duration at enrollment was 1824.0 days. Twenty-three patients with PRU ≥ 208 at enrollment were randomly assigned into either continuing to receive clopidogrel (Continued Group; n = 11) or switching to prasugrel (Switched Group; n = 12). The primary endpoint was the rate of patients who achieved PRU < 208 at the end of 12 weeks of treatment, which was significantly higher in Switched Group relative to Continued Group (90.0% vs. 36.4%; P = 0.024). The secondary endpoint was the PRU at week 12 in groups subdivided according to cytochrome P450 (CYP) 2C19 genotypes. At week 12, extensive metabolizers (EM Group) had 202.3 ± 60.0 and 174.5 ± 22.3 in Continued Group and Switched Group (P = 0.591), respectively; intermediate and poor metabolizers (non-EM Group) had 229.4 ± 36.9 and 148.4 ± 48.4 in Continued Group and Switched Group (P = 0.002), respectively. The PRU for non-EM Group was significantly reduced in Switched Group. Thus, for patients with long-term DAPT (aspirin + clopidogrel) after PCI with coronary stent implantation, switching from clopidogrel to prasugrel resulted in a stable reduction in PRU, regardless of CYP2C19 polymorphism.

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Correlation Between the CYP2C19 Phenotype Status and the Results of Three Different Platelet Function Tests in Cardiovascular Disease Patients Receiving Antiplatelet Therapy: An Emphasis on Newly Introduced Platelet Function Analyzer-200 P2Y Test

Cited by 16 publications

References 24 publications

East Asian perspective on the interaction between proton pump inhibitors and clopidogrel

East Asian perspective on the interaction between proton pump inhibitors and clopidogrel

Novel Strategies for Assessing Platelet Reactivity

Prasugrel effectively reduces the platelet reactivity units in patients with genetically metabolic dysfunction of cytochrome P450 2C19 who are treated with long-term dual antiplatelet therapy after undergoing drug-eluting stent implantation

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