Influence of Cyp2c19*2 Gene Variant on Therapeutic Response During Clopidogrel Treatment in Patients with Carotid Artery Stenosis.

Background: Despite the proven clinical effect of oral antiplatelet drugs, a considerable number of patients do not have an adequate response to clopidogrel. The aim of our study was to determine the influence of loss-of-function variant allele on clopidogrel responsiveness in patients with carotid artery stenosis.

Methods: One hundred and twelve patients with carotid artery stenosis undergoing endarterectomy were included in this one-year prospective study. All of them received clopidogrel (75 mg daily) for at least 30 days after the intervention. They were followed from the moment of hospital admission. genotyping was performed by TaqMan Assay. The influence of variant allele on clopidogrel platelet reactivity was determined using multiple-electrode aggregometry (MEA).

Results: Genotyping results showed that 82 (73.2%) patients were homozygous for wild type, 29 (25.9%) were heterozygous for the allele and 1 (0.9%) was homozygous. After 24 hours, among those with the wild type 29.3% were clopidogrel responders, and in those with the alleles 10%. In the wild type group, 74.4% were clopidogrel responders after 7 days of taking the drug; 82.9% after 30 days of clopidogrel introduction, respectively. In patients with the alleles the number of responders increased up to 46.7% after 7 days; 53.3% after 30 days of taking the drug, respectively. The risk for being a low-responder is higher for the patients heterozygous for the allele vs. wild-type (OR 4.250, 95% CI 1.695-10.658, P<0.01).

Conclusions: The loss-of-function variant allele has significant influence on clopidogrel response in patients with carotid artery stenosis undergoing endarterectomy.