Abstract
SummaryBackgroundDespite 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 CYP2C19*2 loss-of-function variant allele on clopidogrel responsiveness in patients with carotid artery stenosis.MethodsOne 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. CYP2C19*2 genotyping was performed by TaqMan Assay. The influence of CYP2C19*2 variant allele on clopidogrel platelet reactivity was determined using multiple-electrode aggregometry (MEA).ResultsGenotyping results showed that 82 (73.2%) patients were homozygous for wild type, 29 (25.9%) were heterozygous for the CYP2C19*2 allele and 1 (0.9%) was CYP2C19*2 homozygous. After 24 hours, among those with the wild type 29.3% were clopidogrel responders, and in those with the CYP2C19*2 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 CYP2C19*2 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 CYP2C19*2 allele vs. wild-type (OR 4.250, 95% CI 1.695-10.658, P<0.01).ConclusionsThe CYP2C19*2 loss-of-function variant allele has significant influence on clopidogrel response in patients with carotid artery stenosis undergoing endarterectomy.
Highlights
Platelets play a key role in the development of thrombotic complications in patients with atherosclerotic vascular disease [1]
Regarding patients undergoing carotid endarterectomy, perioperative antithrombotic therapy should consist of aspirin alone, while the addition of clopidogrel should be considered for high risk patients [3]
To the best of our knowledge, this is the first study in which the laboratory response to clopidogrel was assessed to evaluate the relationship between the CYP2C19*2 loss-of-function allele and platelet aggregation in patients with carotid artery stenosis undergoing carotid artery stenosis undergoing elective endarterectomy (CEA), who received antiplatelet treatment with clopidogrel
Summary
Platelets play a key role in the development of thrombotic complications in patients with atherosclerotic vascular disease [1]. Aspirin and clopidogrel are the cornerstone therapy in conditions characterized by risk for arterial thrombosis [1]. They are widely used as treatment for patients with acute coronary syndrome and for stent thrombosis prevention in patients undergoing percutaneous coronary intervention [2]. Regarding patients undergoing carotid endarterectomy, perioperative antithrombotic therapy should consist of aspirin alone, while the addition of clopidogrel should be considered for high risk patients [3]. Despite their proven clinical effect, a considerable number of patients do not have an adequate response to aspirin, clopidogrel or both [4]. Ten to fifteen percent of patients receiving these medications have recurrent atherothrombotic events while receiving treatment [2, 5]
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