Medications to prevent additional stroke may be less effective for patients with certain gene variants

In a study published online by JAMA, Yongjun Wang, M.D., of Capital Medical University, Beijing, and colleagues examined the association between variants of the gene CYP2C19 and clinical outcomes of clopidogrel-treated patients with minor stroke or transient ischemic attack. The study is being released to coincide with its presentation at the Second Annual Scientific Session of the Chinese Stroke Association and the Tiantan International Stroke Conference in Beijing.

The Clopidogrel in High-Risk Patients with Acute Nondisabling Cerebrovascular Events (CHANCE) trial showed that the combination of clopidogrel with aspirin compared with aspirin alone reduced the risk of stroke among patients with transient ischemic attack (TIA) or minor ischemic stroke who can be treated within 24 hours after the onset of symptoms. Clopidogrel, in combination with aspirin, has become a recommended treatment option for patients with TIA or acute minor stroke. Variations of the CYP2C19 gene have 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.

For this study, three CYP2C19 major variants were genotyped among 2,933 Chinese patients who were enrolled in the CHANCE trial. Overall, 1,207 patients (41 percent) were noncarriers and 1,726 patients (59 percent) were carriers of CYP2C19 variants. After day 90 follow-up, clopidogrel-aspirin reduced the rate of new stroke in the noncarriers but not in the carriers of the variants (events among noncarriers, 41[6.7 percent] with clopidogrel-aspirin vs 74 [12 percent] with aspirin; events among carriers, 80 [9.4 percent] with clopidogrel-aspirin vs 94 [11 percent] with aspirin).

Similar results were observed for the secondary efficacy outcome (a composite of vascular events [ischemic stroke, hemorrhagic stroke, myocardial infarction, or vascular death]). The effect of treatment assignment on bleeding did not vary significantly between the carriers and the noncarriers of the genetic variants.

“These findings support a role of CYP2C19 genotype in the efficacy of this treatment,” the authors write.

The researchers note that 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.

Article: Association Between CYP2C19 Loss-of-Function Allele Status and Efficacy of Clopidogrel for Risk Reduction Among Patients With Minor Stroke or Transient Ischemic Attack, Yilong Wang, MD, PhD et al., JAMA, doi:10.1001/jama.2016. 8662, published online 23 June 2016.

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