Clopidogrel response

Clopidogrel is a thienopyridine antiplatelet agent that prevents platelet activation and aggregation by irreversibly inhibiting the P2Y12 ADP receptors. As a pro-drug, clopidogrel requires hepatic biotransformation to form an active metabolite. This conversion is composed of two sequential oxidative steps, which involve cytochrome P450-2C19 (CYP2C19) and other enzymes. Genetic variants in CYP2C19 such as CYP2C19*2, along with other genetic and non-genetic factors, are known to influence variability in clopidogrel response. Specific CYP2C19 variants impair formation of the active clopidogrel metabolite, which results in reduced platelet inhibition. Among clopidogrel-treated patients with acute coronary syndromes (ACSs) undergoing percutaneous coronary intervention (PCI), patients with specific variants in the CYP2C19 gene might be at increased risk for serious adverse cardiovascular events and may benefit from an alternative antiplatelet therapy as compared to patients without these variants. Guidelines regarding the use of pharmacogenomic tests in dosing for clopidogrel have been published in Clinical Pharmacology and Therapeutics by the Clinical Pharmacogenetics Implementation Consortium (CPIC) and are available on the PharmGKB website.

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