Clopidogrel May Not Reduce Stroke Risk in Carriers of Certain CYP2C19 Alleles

Very limited data are available addressing the effect of CYP2C19 variants on clopidogrel efficacy in stroke, especially in Asian populations.

Researchers have found that in patients who have had a minor stroke or transient ischemic attack, clopidogrel may not reduce the risk of additional strokes in those who are carriers of CYP2C19 loss-of-function alleles.

The Clopidogrel in High-Risk Patients with Acute Nondisabling Cerebrovascular Events (CHANCE) trial showed that treatment with clopidogrel plus aspirin compared with aspirin alone reduced the risk of stroke in patients with transient ischemic attack (TIA) or minor ischemic stroke who could be treated within 24 hours after symptom onset.

However, despite polymorphisms of the CYP2C19 gene (OMIM 124020) having been identified as strong predictors of clopidogrel nonresponsiveness, “very limited data are available addressing the effect of CYP2C19 variants on clopidogrel efficacy in stroke, especially in Asian populations, in which the rates of stroke incidence and mortality are higher compared with white populations,” wrote Yilong Wang, MD, PhD, of Beijing Tiantan Hospital at Capital Medical University in Beijing, and colleagues. “The prevalence of CYP2C19 loss-of-function variants is also high in Asian populations.”

The researchers genotyped 3 CYP2C19 major alleles (*2, *3, *17) among 2933 Chinese participants (66.4% men, mean age 62.4 years) from 73 locations who were enrolled in the CHANCE randomized trial conducted between January 2, 2010 to March 20, 2012.

The researchers found that 1207 participants (41.2%) were noncarriers, and that 1726 participants (58.8%) were carriers of loss of function alleles (*2, *3).

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After 90 day follow-up, clopidogrel-aspirin reduced the rate of new stroke in noncarriers, but not in carriers of the gene variants: there were 41 events (6.7%) among noncarriers treated with clopidogrel-aspirin; 74 events (12%) among noncarriers treated with aspirin; 80 events (9.4%) among carriers treated with clopidogrel-aspirin; and 94 events (11%) among carriers treated with aspirin.

Similar results were found for the secondary outcome of a composite of vascular events, including ischemic stroke, hemorrhagic stroke, myocardial infarction, or vascular death. The rate of bleeding in the clopidogrel-aspirin group vs aspirin-only group did not vary significantly.

“These findings support a role of CYP2C19 genotype in the efficacy of this treatment,” the authors noted. However, “it will be important

to compare the association of CYP2C19 variants with efficacy of clopidogrel in a different population before applying these results to non-Asian populations, particularly given the variability in results of cardiovascular studies,” they concluded.


Wang Y, Zhao X, Lin J, et al. Association Between CYP2C19 Loss-of-Function Allele Status and Efficacy of Clopidogrel for Risk Reduction Among Patients With Minor Stroke or Transient Ischemic Attack. JAMA. 2016; doi:10.1001/jama.2016.8662.