Reduced Clopidogrel Metabolism in a Multiethnic Population: Prevalence and Rates of Recurrent Cerebrovascular Events

Spokoyny, Ilana; Barazangi, Nobl; Jaramillo, Victor; Rose, Jim; Chen, Charlene; Wong, Christine; Tong, David

doi:10.1016/j.jstrokecerebrovasdis.2013.06.008

Cited by 24 publications

(18 citation statements)

References 17 publications

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“…[40][41][42] A study in 625 Chinese ischemic stroke patients found that CYP2C19 loss-of-function allele carriers had a higher risk of subsequent vascular events versus noncarriers (hazard ratio 2.16 [95% CI 1.31 to 3.56]). 40 Similar results were observed in a smaller study of 53 patients with stroke or transient ischemic attack, 41 and a study of 259 Chinese ischemic stroke patients showed that CYP2C19 loss-of-function allele carriers had poorer functional outcomes, using the National Institutes of Health Stroke Scale and the modified Rankin Scale, compared with noncarriers. 42 These studies, however, were not specific to subcortical events and likely included many individuals with atherosclerotic large artery or cardioembolic mechanisms.…”

Section: Discussionmentioning

confidence: 99%

CYP2C19 Metabolizer Status and Clopidogrel Efficacy in the Secondary Prevention of Small Subcortical Strokes (SPS3) Study

McDonough

McClure

Mitchell

et al. 2015

JAHA

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BackgroundThe role of the CYP2C19 genotype on clopidogrel efficacy has been studied widely, with data suggesting reduced clopidogrel efficacy in loss-of-function variant carriers taking clopidogrel after percutaneous coronary intervention; however, data are limited regarding the association between CYP2C19 genetic variants and outcomes in stroke patients. We investigated whether CYP2C19 metabolizer status affects the risk of recurrent stroke or major bleeding in subcortical stroke patients taking dual antiplatelet therapy with aspirin and clopidogrel.Methods and ResultsCYP2C19*2 and CYP2C19*17 were genotyped in 522 patients treated with dual antiplatelet therapy from the Secondary Prevention of Small Subcortical Strokes (SPS3) study. CYP2C19 metabolizer status was inferred from genotype, and associations with the risk of recurrent stroke and major bleeding were assessed in the overall cohort and by race/ethnic group with logistic regression modeling. In the overall cohort, there were no differences in outcomes by CYP2C19 metabolizer status (recurrent stroke, odds ratio 1.81 [95% CI 0.76 to 4.30]; major bleeding, odds ratio 0.67 [95% CI 0.22 to 2.03]). In white participants, those with CYP2C19 intermediate or poor metabolizer status had higher odds of recurrent stroke (odds ratio 5.19 [95% CI 1.08 to 24.90]) than those with extensive or ultrarapid metabolizer status, but there was no evidence of difference in major bleeding.ConclusionsThere were significant differences in recurrent stroke by CYP2C19 genotype-inferred metabolizer status in white subcortical stroke patients receiving dual antiplatelet therapy with aspirin and clopidogrel, consistent with cardiovascular studies on CYP2C19 and clopidogrel; however, the bleeding risk that led to early termination of the antiplatelet arm of the SPS3 trial does not appear to be explained by CYP2C19 genotype. This study was relatively underpowered; therefore, these findings should be interpreted with caution and warrant replication.Clinical Trial RegistrationURL: http://www.clinicaltrials.gov. Unique identifier: NCT00059306.

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Section: Discussionmentioning

confidence: 99%

CYP2C19 Metabolizer Status and Clopidogrel Efficacy in the Secondary Prevention of Small Subcortical Strokes (SPS3) Study

McDonough

McClure

Mitchell

et al. 2015

JAHA

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“…Although various studies have demonstrated clopidogrel resistance since its discovery in 2003, the exact mechanism is yet to be elucidated (24)(25)(26). Flow cytometry has been used to detect platelet activity (27,28), however clopidogrel resistance remains poorly defined.…”

Section: Discussionmentioning

confidence: 99%

Expression of miRNA-26a in platelets is associated with clopidogrel resistance following coronary stenting

Chen¹,

Qi²,

Chen³

et al. 2016

Experimental and Therapeutic Medicine

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“…Clopidogrel is a common antiplatelet aggregation drug in clinical practice and plays an important role in treating of IS [6] . However, with the increase of clinical application, the e cacy of clopidogrel varies with some patients displaying resistance [7][8][9][10] . Studies have shown that the CYP2C19 gene polymorphism is closely related to the inhibition of clopidogrel on platelets aggregation.…”

Section: Introductionmentioning

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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Reduced Clopidogrel Metabolism in a Multiethnic Population: Prevalence and Rates of Recurrent Cerebrovascular Events

Cited by 24 publications

References 17 publications

CYP2C19 Metabolizer Status and Clopidogrel Efficacy in the Secondary Prevention of Small Subcortical Strokes (SPS3) Study

CYP2C19 Metabolizer Status and Clopidogrel Efficacy in the Secondary Prevention of Small Subcortical Strokes (SPS3) Study

Expression of miRNA-26a in platelets is associated with clopidogrel resistance following coronary stenting

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

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