Impact of Glycemic Control on Efficacy of Clopidogrel in Transient Ischemic Attack or Minor Stroke Patients With CYP2C19 Genetic Variants

Background and Purpose— Dysglycemia may influence the predictive value of CYP2C19 loss-of-function allele for clinical efficacy of antiplatelet drug, but the role of glycated albumin (GA) remains unclear in patients with stroke on antiplatelet drugs. Methods— The CHANCE trial (Clopidogrel in High-Risk Patients With Acute Nondisabling Cerebrovascular Events) included 2933 patients who had GA levels and CYP2C19 genotyping. Cox proportional hazards model was used to assess the interaction between CYP2C19 loss-of-function allele (*2, *3) carrier status and the effect of antiplatelet therapy based on their GA levels. Results— There was significant interaction between carrier status and antiplatelet therapy regimen on the risk of recurrent stroke ( P =0.03) in patients with GA levels of ≤15.5%, but not in those with GA levels of >15.5% ( P =0.48). Only in noncarriers with low GA levels, dual-antiplatelet therapy reduced stroke recurrence (3.5%) compared with those on aspirin alone (14.7%; hazard ratio, 0.23; 95% confidence interval, 0.10–0.49; P <0.001). Similar effects were observed when examined the combined vascular event or ischemic stroke. No significant difference in bleeding was found among groups. Conclusions— In patients with minor stroke or high-risk transient ischemic attack, clopidogrel–aspirin when compared with aspirin alone reduced stroke recurrence only in noncarriers of CYP2C19 loss-of-function allele and normal GA levels. Clinical Trial Registration— URL: http://www.clinicaltrials.gov . Unique identifier: NCT00979589.