Relationship between cytochrome P450 2C19 polymorphisms and clinical outcomes in clopidogrel-treated patients who underwent cerebrovascular stenting placement

Objective To evaluate the impact of cytochrome P450 (CYP) 2C19 gene polymorphisms on clinical outcome in clopidogrel-treated patients who underwent cerebrovascular stenting placement. Methods One hundred and ninty-four patients who underwent cerebrovascular stent placement and with long-term treatment of clopidogrel (75 mg/d) between April 2009 and December 2010 were enrolled，CYP2C19 genotype was detected by improved multiple ligase detection reaction.The primary clinical endpoints were ischemic stroke and death after stent implantation; the key secondary endpoints were hemorrhagic stroke and other vascular events. Results The average followed-up was (19.4±9.9) months.The overall incidence of primary endpoints was 16.5%.Of the 194 patients，87 (44.8%) were wild-type homozygous，88 (45.4%) were heterozygotes，and 19 (9.8%) were homozygous.The cumulative incidence of adverse outcomes was significant higher in CYP2C192 carrier than that in noncarriers (22.4% (24/107) vs 9.2% (8/87)，HR=2.74，95% CI 1.23-6.10，P=0.01).Of the 194 patients，13 (6.7%) were heterozygotes，and 181 (93.3%) were wild-type homozygous.CYP2C193 polymorphism had no significant impact on the outcomes in this cohort of patients.No relationship between gene and the secondary endpoints were detected.After multivariable analysis，the CYP2C192 was an independent predictor of clinical outcomes of cerebrovascular stent placement (HR=2.89，95% CI 1.10-7.60，P=0.03). Conclusions CYP2C192 is an independent determinant of adverse events after cerebrovascular stent placement treated with clopidogrel.While CYP2C193 is not associated with the clinical prognosis in patients with cerebrovascular stent placement. Key words: Brain ischemia; Stroke; Aryl hydrocarbon hydroxylases; Polymorphism，genetic; Stents; Ticlopidine; Prognosis