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

Abstract

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.

Keywords: clopidogrel; cytochrome P-450 CYP2C19; glycosylated serum albumin; ischemic attack, transient; stroke.