The secondary prevention of stroke according to cytochrome P450 2C19 genotype in patients with acute large-artery atherosclerosis stroke

PURPOSE: To investigated the effectiveness of antiplatelet agents for the secondary prevention of stroke according to CYP2C19 genotype in patients with ischemic stroke (IS). METHODS: Between August 2009 and December 2011, 570 acute IS patients with acute large-artery atherosclerosis were randomly assigned to receive either combined clopidogrel and aspirin for the first 30 day, and clopidogrel thereafter (clopidogrel group, n=284) or aspirin monotherapy (aspirin group, n=286). CYP2C19 genotypes were measured and masked until the end-of-study. The primary outcome was a composite of IS, transient ischemic attack (TIA), myocardial infarction (MI), and death. RESULTS: During the 5 years follow-up, the primary outcome occurred in 105 patients (18.4%) (71 had IS, 10 had TIA, 12 had MI, and 12 died). There were no significant differences in the primary outcome between clopidogrel group and aspirin group (16.5% vs. 20.3%) or between carriers of the CYP2C19 reduced-function alleles and noncarriers (21.8% vs.15.7%). In patients with aspirin therapy, CYP2C19 polymorphism was not associated with the primary outcome. However, in patients treated with clopidogrel, carriers of at least one CYP2C19 reduced-function allele had a 3-fold higher adjusted risk for primary outcome compared with noncarriers (95% confidence interval, 1.23 to 8.74). CONCLUSIONS: Among IS patients treated with clopidogrel, carriers of a reduced-function CYP2C19 allele had a significantly higher rate of adverse vascular events than did noncarriers. It should avoid prescribing clopidogrel to these patients with known CYP2C19 polymorphisms.