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 transient ischemic attack (TIA) or minor ischemic stroke. They found that the combination of clopidogrel with aspirin compared with aspirin alone reduced the risk of subsequent stroke among carriers of the CYP2C19 genotype who were treated within 24 hours after the onset of symptoms.

The results were part of the Clopidogrel in High-Risk Patients with Acute Nondisabling Cerebrovascular Events (CHANCE) trial.  It 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.

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.

The study is supported by grants from the Ministry of Science and Technology of the People's Republic of China, the Beijing Biobank of Cerebral Vascular Disease, the Beijing Institute for Brain Disorders, the National Natural Science Foundation of China (No. 81322019), the China Postdoctoral Science Foundation, the Natural Science Foundation of Fujian Province, the Beijing Municipal Science and Technology Commission, and the Shanghai Municipal Commission of Health and Family Planning and supported from the Ellrodt-Schweighauser Family Chair of Cancer Genomic Research of NorthShore University Health System.