Key result
Genetic variants of CYP2C19, particularly the *2 loss-of-function allele, significantly reduce clopidogrel active metabolite generation and platelet inhibition, leading to increased risk of ischemic events.
Why the study?
How do genetic polymorphisms of CYP2C19 and ABCB1 affect the clinical efficacy and safety of clopidogrel in patients with coronary artery disease?
How do genetic polymorphisms of CYP2C19 and ABCB1 affect the clinical efficacy and safety of clopidogrel in patients with coronary artery disease?
Genetic testing for CYP2C19 polymorphisms may help predict ischemic and bleeding risks in CAD patients treated with clopidogrel.
Answers are grounded in this paper and cite their sources.
Supports pharmacogenetic risk stratification with clopidogrel; leaves open whether CYP2C19-guided therapy improves CAD outcomes.
Antiplatelet agents are the mainstay treatment in the prevention and management of atherothrombotic complications. However, a substantial interpatient variability in response to clopidogrel has been reported. Furthermore, patients with coronary artery disease and lesser platelet inhibition in response to clopidogrel are at increased risk for cardiovascular events. Clopidogrel after absorption requires two-step oxidation by the hepatic cytochrome P450 to generate its active metabolite. Polymorphisms of genes encoding the cytochrome enzymes and P-glycoprotein involved in clopidogrel absorption are regarded as major determinants of the interindividual variability in the clopidogrel-induced platelet inhibition. In our review we discuss the prevalence and clinical significance of various alleles of the genes: CYP2C19 and ABCB1 in the setting of coronary artery disease. Allele CYP2C19*2 is associated with excess of ischaemic events including myocardial infarction and stent thrombosis. On the other hand, CYP2C19*17 allele poses a serious threat of bleeding. Data concerning the prognostic value of genetic variant 3435C→T of ABCB1 remain inconclusive.
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Kubica et al. (2011) conducted a review in Coronary artery disease. CYP2C19 and ABCB1 polymorphisms vs. Wild-type genotype was evaluated. Genetic variants of CYP2C19, particularly the *2 loss-of-function allele, significantly reduce clopidogrel active metabolite generation and platelet inhibition, leading to increased risk of ischemic events.
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