CYP2C19 Genotype and Early Ischemic Lesion Recurrence in Stroke Patients Treated with Clopidogrel

Jeong, Tae Dong; Kim, Seung Min; Kim, Hyo Jin; Lee, Woochang; Kwon, Sun U.; Min, Won Ki; Kang, Dong Wha; Chun, Sail

doi:10.1016/j.jstrokecerebrovasdis.2014.09.014

Cited by 25 publications

(20 citation statements)

References 27 publications

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“…11,20 Moreover, 10 of 11 (90.9%) studies that recruited subjects within 1 week after the index stroke demonstrated significant associations with CYP2C19 variants. [8][9][10][11][12][16][17][18][19][20] In contrast, none of 3 studies that recruited subjects within >2 weeks of the index stroke showed significant relationships. In a cardiological study, Arima et al…”

Section: Discussionmentioning

confidence: 99%

“…[13][14][15] To address these inconsistent results, we hypothesized that differences in the elapsed time from stroke onset might affect the relationship between the genetic variants and cardiovascular events because most studies enrolled stroke patients in the acute phase (within 1 week of the index of stroke). [8][9][10][11][12][15][16][17][18][19][20] We therefore prospectively investigated whether CYP2C19 variants affected cardiovascular events during 2 years of follow-up in the chronic phase of stroke.…”

Section: Vasodilator-stimulated Phosphoprotein (Vasp) Index Analysismentioning

confidence: 99%

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Association of <i>CYP2C19</i> Polymorphisms With Clopidogrel Reactivity and Clinical Outcomes in Chronic Ischemic Stroke

Yamagami

Ihara

Miyata

et al. 2019

Circ J

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Background: CYP2C19 variants are associated with the antiplatelet effects of clopidogrel against recurrent cardiovascular events. However, it remains unknown whether the elapsed time from stroke onset affects the relationship between the genetic variants and such events. To address this, we conducted a prospective cohort study to determine the effect of CYP2C19 variants on clinical outcomes in the chronic phase. Methods and Results: In total, 518 Japanese non-acute stroke patients treated with clopidogrel were registered at 14 institutions. Patients were classified into 3 clopidogrel-metabolizing groups according to CYP2C19 genotype: extensive metabolizer (EM: *1/*1), intermediate metabolizer (IM: *1/*2 or *1/*3), and poor metabolizer (PM: *2/*2, *2/*3, or *3/*3). Antiplatelet effects of clopidogrel were assessed by adenosine diphosphate (ADP)-induced platelet aggregation and vasodilator-stimulated phosphoprotein (VASP) phosphorylation. The endpoint was composite cerebrocardiovascular events (CVEs). In 501 successfully followed-up patients, the median time from index stroke to enrollment was 181 days. There were 28 cardiovascular and 2 major bleeding events. There were no significant differences in the rates of cardiovascular events among the groups. Conclusions: Despite associations between CYP2C19 variants and on-clopidogrel platelet reactivity, there was no significant difference in rates of CVEs in the chronic stroke phase among the 3 clopidogrel-metabolizing groups of CYP2C19 variants.

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Section: Discussionmentioning

confidence: 99%

Section: Vasodilator-stimulated Phosphoprotein (Vasp) Index Analysismentioning

confidence: 99%

Association of <i>CYP2C19</i> Polymorphisms With Clopidogrel Reactivity and Clinical Outcomes in Chronic Ischemic Stroke

Yamagami

Ihara

Miyata

et al. 2019

Circ J

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“…Patients are categorized by CYP2C19 metabolizer status based on *2, *3, and *17 genotypes using the common consensus star allele nomenclature. CYP2C19*2, *3 are loss-of-function alleles, and CYP2C19*17 is gain-of-function allele [30] . those without loss-of-function allele (*1/*1) are classi ed as extensive metabolizers [31] .…”

Section: Cyp2c19 Genotype and 11-dhtxb2 Testsmentioning

confidence: 99%

Effect of precision antiplatelet therapy based on CYP2C19/11-dhTxB2 variability in prognosis of ischemic stroke/TIA patients: study protocol for a multicenter randomized controlled trial

Wang

Kuang

et al. 2020

Preprint

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Abstract Background: Clopidogrel and aspirin are conventional drugs for treating ischemic stroke (IS) and transient ischemic attack (TIA). However, with the increase of clinical application, many patients have shown clopidogrel resistance and/or aspirin resistance . clopidogrel resistance is related with cytochrome P450-2C19 (CYP2C19) poly m orphism , and aspirin resistance is related to urine concentration of 11-dehydroxetane B2. At present, the effect of precision antiplatelet medication based on the cytochrome CYP2C19 genotype test and the 11-dhTxB2 test has not been evaluated prospectively in a large sample. Methods: This is a randomized controlled trial evaluating the effects of precision antiplatelet medication based on the CYP2C19 genotype test and the 11-dhTxB2 test on IS/TIA patients over 12 months. Outcomes of interest including stroke recurrence, neurologic disabilities defined by the Modified Rankin Scale (mRS), bleeding events, other adverse events, and all-cause mortality will be assessed at the 1st, 3rd, 6th and 12th-month post-discharge. Demographics, risk factors, laboratory investigations, medications, physiological tests, and brain imaging will also be assessed. Discussion: Some stroke patients have resistance to clopidogrel or aspirin, but there is still no personalized medicine. Our study will conduct free antiplatelet resistance tests and individualized antiplatelet medication for patients in the intervention group, ultimately evaluating individualized medication effectiveness through a one-year follow-up. The research results will help to assess the impact of personalized antiplatelet drug therapy on the prognosis of stroke, thus providing a reference for precise clinical treatment. Trial registration: Chinese Clinical Trial Registry, ChiCTR1900026492. Registered on 12 October 2019.

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“…[30,31] . Those with at least 1 loss-of-function allele (*2 or *3) are classified as loss-of-function allele carriers and those with at least 1 gain-of-function allele (*17) are classified as gain-of-function allele carriers [32] .…”

Section: Cyp2c19 Genotyping and 11-dhtxb2 Testingmentioning

confidence: 99%

Effects of precision antiplatelet therapy based on CYP2C19/11-dhTxB2 variability in prognosis of ischemic stroke/TIA patients: study protocol for a multicenter randomized controlled trial

Wang

Kuang

et al. 2020

Preprint

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IntroductionClopidogrel and aspirin are routine drugs for the treatment of ischemic stroke (IS) and transient ischemic attack (TIA). However, with the increase of clinical application, a large number of patients have displayed clopidogrel resistance and/or aspirin resistance. At present, the effect of genetically tailored medication has not been prospective evaluated in a large sample.Methods and analysisThis study is an investigator-initiated, multicentre, large sample, prospectively, randomized controlled study evaluating the effects of precision antiplatelet medication based on the cytochrome P450 2C19 (CYP2C19) genetic test and the 11-dehydroxetane B2 (11-dhTxB2) test on IS/TIA patients over a duration of 12 months. Outcomes of interest including stroke recurrence, neurologic disabilities defined by the Modified Rankin Scale (mRS), bleeding events, other adverse events, and all-cause mortality will be assessed at the 1st, 3rd, 6th and 12th month post discharge. Demographics, risk factors, laboratory investigations, medications, physiological tests, and brain imaging will be assessed as well.Ethics and disseminationThe study was approved by the Medical Ethics Committee of the Second Affiliated Hospital of Nanchang University: (2018) Medical Research Review No.05. In this study, a pre-experiment was carried out in April 2019. Formal recruitment of patients began in June 2019 and will continue until December 2020. Participants will be followed for one-year and the study will end in December 2021. The results of the study will be disseminated through peer-reviewed publications and conference reports.Trial registration numberChiCTR1900026492.Trial registration date2019.10.12Trial registry name“Establishment of intelligent decision-making system for treatment of neurological impairment in cerebrovascular disease”. Tt is a prospectively study.Protocol versionV5.0, 2019/02/19.

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CYP2C19 Genotype and Early Ischemic Lesion Recurrence in Stroke Patients Treated with Clopidogrel

Cited by 25 publications

References 27 publications

Association of <i>CYP2C19</i> Polymorphisms With Clopidogrel Reactivity and Clinical Outcomes in Chronic Ischemic Stroke

Association of <i>CYP2C19</i> Polymorphisms With Clopidogrel Reactivity and Clinical Outcomes in Chronic Ischemic Stroke

Effect of precision antiplatelet therapy based on CYP2C19/11-dhTxB2 variability in prognosis of ischemic stroke/TIA patients: study protocol for a multicenter randomized controlled trial

Effects of precision antiplatelet therapy based on CYP2C19/11-dhTxB2 variability in prognosis of ischemic stroke/TIA patients: study protocol for a multicenter randomized controlled trial

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