Impact of CYP2C19 polymorphism on residual platelet reactivity in patients with coronary heart disease during antiplatelet therapy

Yamamoto, Koichiro; Hokimoto, Seiji; Chitose, Tadasuke; Morita, Kazunori; Ono, Tetsuya; Kaikita, Koichi; Tsujita, Kenichi; Abe, Tomohide; Deguchi, Mariko; Miyagawa, Hiroshi; Saruwatari, Junji; Sumida, Hitoshi; Sugiyama, Seigo; Nakagawa, Kazuko; Ogawa, Hisao

doi:10.1016/j.jjcc.2010.10.007

Cited by 92 publications

(69 citation statements)

References 25 publications

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“…CYP2C19 has been reported to contain several polymorphisms which are more frequent in Asian populations, particularly in the Japanese population. 3,8) Indeed, in Japanese populations, 37% are EMs, 44% are IMs, and 19% are PMs.…”

Section: Discussionmentioning

confidence: 99%

Dual Antiplatelet Therapy Guided by <i>CYP2C19</i> Polymorphisms after Implantation of Second-Generation Drug-Eluting Stents for Management of Acute Coronary Syndrome

et al. 2018

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SummaryPrasugrel, a novel P2Y12 receptor inhibitor, is administered to patients with acute coronary syndrome (ACS) after percutaneous coronary intervention (PCI), but it can increase the risk of bleeding. The Japanese exhibit weaker responses to clopidogrel than other races because of CYP2C19 polymorphisms; thus, it is unclear whether these patients should continue dual antiplatelet therapy (DAPT) using prasugrel or switch to clopidogrel in the chronic phase. Here we evaluated the clinical outcomes of DAPT guided by CYP2C19 polymorphisms after implantation of second-generation drug-eluting stents (DESs) for ACS management. Patients with ACS receiving PCI via DES from November 2011 to March 2015 were divided into two groups: conventional DAPT with clopidogrel (n = 41) and gene-guided DAPT (n = 24). In the gene-guided DAPT group, all patients with ACS were given DAPT using prasugrel as soon as possible; extensive and intermediate metabolizers receiving PCI for the first time were switched to clopidogrel at least 2 weeks after discharge, and intermediate metabolizers with repeated ACS and poor metabolizers continued on DAPT using prasugrel. Notably, geneguided DAPT significantly reduced major adverse cardiovascular/cerebrovascular events (MACCEs; 22.0% versus 4.2%, hazard ratio [HR]: 0.15, 95% confidence interval [CI]: 0.01-0.81; P = 0.0247). Hemorrhagic complications were observed in 3.1% of patients receiving conventional DAPT and absent in the gene-guided group. Moreover, multivariate analysis showed that gene-guided DAPT significantly decreased MACCE incidence (HR: 0.15, 95% CI: 0.01-0.81; P = 0.033). Collectively, these data suggest that CYP2C19 polymorphism analysis may improve treatment decisions in patients with ACS receiving DES-PCI.(Int Heart J 2018; 59: 21-26) Key words: Prasugrel, Clopidogrel, Percutaneous coronary intervention (PCI), Major adverse cardiovascular/ cerebrovascular event (MACCE) P ercutaneous coronary intervention (PCI) is the first-line therapy for acute coronary syndrome (ACS), and drug-eluting stents (DESs) have been widely employed with excellent results in patients with stable coronary artery disease (CAD) or ACS.1,2) However, Japanese individuals exhibit weaker responses to clopidogrel, a classic P2Y12 receptor inhibitor, owing to an increased incidence of CYP2C19 loss-of-function polymorphisms.3) Recent reports have established the efficacy of prasugrel, a novel P2Y12 receptor inhibitor exhibiting strong inhibition of platelet aggregation, in patients with ACS after PCI independent of CYP2C19 function.4) However, prasugrel may increase the risk of bleeding, 5) and it is unknown whether patients with ACS should continue dual antiplatelet therapy (DAPT) using prasugrel or be switched to DAPT using clopidogrel during the chronic phase.In this study, we evaluated 1-year clinical outcomes of patients receiving CYP2C19 polymorphism-guided DAPT after implantation of second-generation DESs for ACS management. Methods Study population:We evaluated consecutive patients with ACS who received ...

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Section: Discussionmentioning

confidence: 99%

Dual Antiplatelet Therapy Guided by <i>CYP2C19</i> Polymorphisms after Implantation of Second-Generation Drug-Eluting Stents for Management of Acute Coronary Syndrome

et al. 2018

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“…It is reported that 56% of Japanese patients have CYP2C19-induced metabolism abnormalities. 21) Based on these findings, Watanabe, et al pointed out that there is a risk associated with administering DAPT to all TAVI patients. In a meta-analysis to study whether P2Y12 reactivity units (PRU) can predict the prognosis, 3059 patients undergoing PCI were analyzed in 6 studies, and a significantly high incidence of complications due to MI or stent thrombosis was reported for patients with PRU ≧ 230.…”

Section: Article P190mentioning

confidence: 99%

Is Dual Antiplatelet Therapy Necessary in Transcatheter Aortic Valve Implantation?

Oguri

Ando

2016

Int. Heart J.

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“…Five meta-analyses did not include conference abstracts, 5,25,[28][29][30] and all but one of the metaanalyses left out data from one or more full articles that were included in other meta-analyses (Supplementary Table S1 and Supplementary Appendix S1 online). [34][35][36][37][38][39][40][41] For example, the post hoc genetic analysis of the ACTIVE-A trial was included in only two of the seven meta-analyses that did their literature searches after the publication of the trial, 6,24 and one meta-analysis had limited the inclusion to only primary studies with a follow-up time of 6-12 months.…”

Section: -30mentioning

confidence: 99%

A systematic review and critical assessment of 11 discordant meta-analyses on reduced-function CYP2C19 genotype and risk of adverse clinical outcomes in clopidogrel users

Osnabrugge

Head

Zijlstra

et al. 2015

Genetics in Medicine

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Clopidogrel, in combination with aspirin, is a standard treatment for patients with acute coronary syndrome and is one of the top-selling drugs in the world.1,2 However, there is substantial interindividual variability in response. Polymorphisms of the cytochrome P450 (CYP) gene have been identified as a potential risk factor for nonresponse.3 This gene plays a central role in drug-metabolizing processes in the liver, and clopidogrel makes use of these processes to transform into an active metabolite capable of inhibiting platelet aggregation. Identification of CYP2C19 polymorphisms could lead to personalized treatment based on genotype in patients with acute coronary syndrome, and therefore, the US Food and Drug Administration recommends CYP2C19 genotyping for individualized antiplatelet management. 4 The association between CYP2C19 loss-of-function alleles and clinical efficacy of clopidogrel has been studied extensively, and several meta-analyses have summarized the results of those studies.5-8 Systematic reviews and meta-analyses are often considered the highest level of evidence, 9-11 and their popularity in the cardiovascular field increased almost 13 times as fast as the increase in number of published randomized clinical trials. 12However, the interpretation of meta-analyses is confusing when the conclusions of overlapping meta-analyses are discordant. Some meta-analyses on CYP2C19 loss-of-function and clinical efficacy of clopidogrel conclude that the association is proven, 7,8 whereas others conclude the opposite. 5,6 Our objective was to systematically evaluate the discordant evidence for the association between CYP2C19 loss-offunction alleles and clinical efficacy of clopidogrel through a critical methodological appraisal of published meta-analyses. MATERIALS AND METHODSOur review adheres to the PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) statement, 13 and we consulted the Cochrane Handbook for Systematic Reviews of Interventions for methodological aspects of meta-analyses. We systematically investigated how 11 overlapping meta-analyses on the association between CYP2C19 loss-of-function alleles and clinical efficacy of clopidogrel could yield contradictory outcomes. The results of the meta-analyses differed because more recent metaanalyses included more primary studies and some had not included conference abstracts. Conclusions differed because between-study heterogeneity and publication bias were handled differently across meta-analyses. All meta-analyses on the clinical end point observed significant heterogeneity and several reported evidence for publication bias, but only one out of eight statistically significant meta-analyses concluded that therefore the association was unproven and one other refrained from quantifying a pooled estimate because of heterogeneity. For the end point stent thrombosis, all meta-analyses reported statistically significant associations with CYP2C19 loss-of-function alleles with no statistically significant evidence for heterogeneity, b...

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Impact of CYP2C19 polymorphism on residual platelet reactivity in patients with coronary heart disease during antiplatelet therapy

Abstract: CYP2C19 polymorphism may be associated with high residual platelet reactivity and the occurrence of cardiovascular events.

Cited by 92 publications

References 25 publications

Dual Antiplatelet Therapy Guided by <i>CYP2C19</i> Polymorphisms after Implantation of Second-Generation Drug-Eluting Stents for Management of Acute Coronary Syndrome

Dual Antiplatelet Therapy Guided by <i>CYP2C19</i> Polymorphisms after Implantation of Second-Generation Drug-Eluting Stents for Management of Acute Coronary Syndrome

Is Dual Antiplatelet Therapy Necessary in Transcatheter Aortic Valve Implantation?

A systematic review and critical assessment of 11 discordant meta-analyses on reduced-function CYP2C19 genotype and risk of adverse clinical outcomes in clopidogrel users

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