Variant recurrent risk among stroke patients with different CYP2C19 phenotypes and treated with clopidogrel. (September 2015)

• Record Type: Journal Article
• Authors: Sun, Wenshan; Li, Yongkun; Li, Junrong; Zhang, Zhizhong; Zhu, Wusheng; Liu, Wenhua; Cai, Qiankun; Wang, Xiaomeng; Cao, Liping; Bai, Wen; Fan, Xinying; Ma, Minmin; Guo, Ruibing; Liu, Xinfeng; Xu, Gelin
• Is Part Of: Platelets. Volume 26:Number 6(2015:Sep.)
• Page Start: 558
• Page End: 562
• Publication Date: 2015-09
• Subjects: Blood platelets -- Periodicals; Blood Platelets -- Periodicals; 615.39
• Languages: English
• ISSNs: 0953-7104

Abstract

<abstract> <title>Abstract</title> <p>Polymorphisms of <italic>CYP2C19</italic> have been associated with variant risk of subsequent cardiovascular events in survivors of myocardial infarction (MI) receiving clopidogrel. This study evaluated the impacts of <italic>CYP2C19</italic> polymorphisms on stroke recurrence and other vascular events in a cohort of Chinese patients receiving clopidogrel. From Nanjing Stroke Registry Program, 625 consecutive patients with ischemic stroke were enrolled between May 2008 and April 2010. <italic>CYP2C19</italic> variants (<italic>*2, *3</italic>, and <italic>*17</italic>) were genotyped. Clinical outcomes were determined with three monthly follow-up. The primary endpoint was a composite of vascular death, non-fatal ischemic stroke, and non-fatal MI. The second endpoint was bleeding events. The median exposure to clopidogrel was 13.2 (interquartile range, 8.9–18.0) months. Primary endpoint was observed in 85 (13.6%) patients and secondary endpoint in 13 (2.1%) patients. Frequencies of <italic>CYP2C19*1, *2, *3</italic>, and <italic>*17</italic> alleles were 61.2, 34.0, 3.8, and 1.0%, respectively, in this patient cohort. <italic>CYP2C19</italic> loss-of-function allele (<italic>*2</italic> and <italic>*3</italic>, LOF) carriers were observed with higher risk of subsequent vascular events compared with non-carriers (17.2 versus 8.1%, HR = 2.16, 95% CI: 1.31–3.56, <italic>p</italic> = 0.003). After adjusted for age, sex, major cardiovascular risk factors, and drug agent, <italic>CYP2C19</italic> LOF carrier was independently associated with primary endpoint (HR = 2.31, 95% CI: 1.39–3.84, <italic>p</italic> = 0.001). No significant association between <italic>CYP2C19</italic> gain-of-function (<italic>*17</italic>, GOF) and clinical events was detected. In Chinese stroke survivors treated with clopidogrel, carriers of <italic>CYP2C19</italic> LOF allele may have increased risk of recurrence.</p> </abstract>