Genetic Polymorphisms and Clopidogrel Efficacy for Acute Ischemic Stroke or Transient Ischemic Attack

Author:

Pan Yuesong1,Chen Weiqi1,Xu Yun1,Yi Xingyang1,Han Yan1,Yang Qingwu1,Li Xin1,Huang Li’an1,Johnston S. Claiborne1,Zhao Xingquan1,Liu Liping1,Zhang Qi1,Wang Guangyao1,Wang Yongjun1,Wang Yilong1

Affiliation:

1. From Department of Neurology, Beijing Tiantan Hospital, Capital Medical University, China (Y.P., W.C., X.Z., L.L., Q.Z., G.W., Yongjun Wang, Yilong Wang); China National Clinical Research Center for Neurological Diseases, Beijing (Y.P., W.C., X.Z., L.L., Q.Z., G.W., Yongjun Wang, Yilong Wang); Center of Stroke, Beijing Institute for Brain Disorders, China (Y.P., W.C., L.H., X.Z., L.L., Q.Z., G.W., Yongjun Wang, Yilong Wang); Beijing Key Laboratory of Translational Medicine for Cerebrovascular...

Abstract

Background: The association of genetic polymorphisms and clopidogrel efficacy in patients with ischemic stroke or transient ischemic attack (TIA) remains controversial. We performed a systematic review and meta-analysis to assess the association between genetic polymorphisms, especially CYP2C19 genotype, and clopidogrel efficacy for ischemic stroke or TIA. Methods: We conducted a comprehensive search of PubMed and EMBASE from their inceptions to June 24, 2016. Studies that reported clopidogrel-treated patients with stroke or TIA and with information on genetic polymorphisms were included. The end points were stroke, composite vascular events, and any bleeding. Results: Among 15 studies of 4762 patients with stroke or TIA treated with clopidogrel, carriers of CYP2C19 loss-of-function alleles (*2, *3, and *8) were at increased risk of stroke in comparison with noncarriers (12.0% versus 5.8%; risk ratio, 1.92, 95% confidence interval, 1.57–2.35; P <0.001). Composite vascular events were also more frequent in carriers of CYP2C19 loss-of-function alleles than in noncarriers (13.7% versus 9.4%; risk ratio, 1.51, 95% confidence interval, 1.10–2.06; P =0.01), whereas bleeding rates were similar (2.4% versus 3.1%; risk ratio, 0.89, 95% confidence interval, 0.58–1.35; P =0.59). There was no evidence of statistical heterogeneity among the included studies for stroke, but there was for composite vascular events. Genetic variants other than CYP2C19 were not associated with clinical outcomes, with the exception that significant associations of PON1 , P2Y12 , and COX-1 with outcomes were observed in 1 study. Conclusions: Carriers of CYP2C19 loss-of-function alleles are at greater risk of stroke and composite vascular events than noncarriers among patients with ischemic stroke or TIA treated with clopidogrel.

Publisher

Ovid Technologies (Wolters Kluwer Health)

Subject

Physiology (medical),Cardiology and Cardiovascular Medicine

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