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

Stroke. 2017 Apr;48(4):998-1004. doi: 10.1161/STROKEAHA.116.016463. Epub 2017 Mar 13.


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: Unique identifier: NCT00979589.

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

Publication types

  • Randomized Controlled Trial

MeSH terms

  • Aged
  • Aspirin / administration & dosage
  • Aspirin / pharmacology*
  • Clopidogrel
  • Cytochrome P-450 CYP2C19 / genetics*
  • Double-Blind Method
  • Female
  • Glycated Serum Albumin
  • Glycation End Products, Advanced
  • Heterozygote
  • Humans
  • Ischemic Attack, Transient* / blood
  • Ischemic Attack, Transient* / drug therapy
  • Ischemic Attack, Transient* / genetics
  • Male
  • Middle Aged
  • Outcome Assessment, Health Care*
  • Platelet Aggregation Inhibitors / administration & dosage
  • Platelet Aggregation Inhibitors / pharmacology*
  • Recurrence
  • Risk
  • Serum Albumin / metabolism*
  • Stroke* / blood
  • Stroke* / drug therapy
  • Stroke* / genetics
  • Stroke* / prevention & control
  • Ticlopidine / administration & dosage
  • Ticlopidine / analogs & derivatives*
  • Ticlopidine / pharmacology


  • Glycation End Products, Advanced
  • Platelet Aggregation Inhibitors
  • Serum Albumin
  • Clopidogrel
  • CYP2C19 protein, human
  • Cytochrome P-450 CYP2C19
  • Ticlopidine
  • Aspirin
  • Glycated Serum Albumin

Associated data