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Genetic variants play role in clopidogrel effectiveness after minor stroke, TIA
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In a subgroup analysis of the CHANCE trial, clopidogrel plus aspirin was only effective in reducing the risk for new stroke after minor stroke or transient ischemic attack in patients who were not carriers of CYP2C19 loss-of-function alleles.
“This study indicated that CYP2C19 loss-of-function carrier genotypes were associated with less protection from subsequent stroke and composite vascular events for patients with acute minor stroke or TIA treated with clopidogrel and aspirin, compared with noncarrier status,” Yongjun Wang, MD, PhD, of the department of neurology, Beijing Tiantan Hospital, Capital Medical University, Beijing, and the China National Clinical Research Center for Neurological Diseases in Beijing, told Cardiology Today. “[A] genotyping test is needed before taking clopidogrel for secondary prevention of stroke. Alternative treatment could be considered for CYP2C19 loss-of-function carriers.”
Wang and colleagues presented the data at the Second Annual Scientific Session of the Chinese Stroke Association and the Tiantan International Stroke Conference and published the results in JAMA.
CHANCE was a randomized, double blind, placebo-controlled multicenter trial conducted in China demonstrating that clopidogrel and aspirin were more effective than aspirin alone in treating patients with TIA or minor ischemic stroke if the medication was given within 24 hours of symptom onset.
Carriers vs. noncarriers
In the present subgroup analysis, three single-nucleotide polymorphisms for CYP2C19 were genotyped in 2,933 patients (mean age, 62 years; 66% men) from the CHANCE trial. Of these, 1,726 (58%) were CYP2C19 loss-of-function carriers; 52.5% of the patients were carriers of the CYP2C19*2 allele and 9% were CYP2C19*3 carriers.
According to the results, clopidogrel plus aspirin reduced risk for new stroke at 90 days compared with aspirin alone in noncarriers but not in carriers of the loss-of-function alleles (rate among noncarriers, 6.7% with clopidogrel-aspirin vs. 12.4% with aspirin; HR = 0.51; 95% CI, 0.35-0.75; rate among carriers, 9.4% with clopidogrel-aspirin vs. 10.8% with aspirin; HR = 0.93; 95% CI, 0.69-1.26; P for interaction = .02).
The treatment effect of clopidogrel-aspirin vs. aspirin alone on the secondary efficacy outcome of ischemic stroke, hemorrhagic stroke, MI or vascular death at 90 days was also greater in noncarriers than in carriers (noncarriers: clopidogrel-aspirin, 6.7%; aspirin, 12.5%; HR = 0.5; 95% CI, 0.34-0.74; carriers: clopidogrel-aspirin, 9.4%; aspirin, 10.9%; HR = 0.92; 95% CI, 0.68-1.24; P for interaction = .02), according to the researchers.
Bleeding not affected
The rate of bleeding did not vary between carriers and noncarriers in the clopidogrel-aspirin group or the aspirin-alone group.
“This study provided evidence supporting genetic testing that may allow clinicians to personalize antiplatelet therapy, especially in East Asian patient populations for whom the prevalence of CYP2C19 loss-of-function allele is high,” the researchers wrote. – by Tracey Romero
References:
Wang Y, et al. Clopidogrel in high-risk patients with acute non-disabling cerebrovascular events. Presented at: Second Annual Scientific Session of the Chinese Stroke Association and the Tiantan International Stroke Conference; June 24-26, 2016; Beijing.
Wang Y, et al. JAMA. 2016; doi:10.1001/jama.2016.8662.
For more information:
Yongjun Wang, MD, PhD, can be reached at No. 6 Tiantanxili, Dongcheng District, Beijing, China 100050; email: yongjunwang1962@gmail.com.
Disclosure: Wang reports no relevant financial disclosures. One researcher reports receiving support from AstraZeneca and Sanofi.