Implementing genotype-guided antithrombotic therapy.

Richard L Seip, Jorge Duconge, Gualberto Ruaño

Journal: Future cardiology 2010;6(3):409-24

PMID: 20462345

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Abstract

Genotyping has the potential to improve the efficacy and safety of major antithrombotic drugs. For warfarin, the stable maintenance dose varies from 1-10 mg/day. The VKORC1 -1639G>A allele and the CYP2C9*2 and *3 alleles (cumulative frequency: 90% in Asians, 65% in Europeans and 20% in Africans), explain 45% of response variability in European and 30% in African populations. The large clinical trials COAG and EU-PACT will define the extent to which pharmacogenetic dosing affects the safety and efficacy of warfarin and coumarin derivatives. The platelet inhibitor clopidogrel requires activation by the CYP2C19 enzyme. CYP2C19*2 and *3 alleles (cumulative frequency: 20-50%) produce null enzyme activity, and their presence attenuates platelet inhibition and increases cardiovascular events. The US FDA-mandated drug labeling recognizes the relevance of genotyping in the selection and dosing of both warfarin and clopidogrel.

Address: Genomas, Inc., 67 Jefferson Street, Hartford, CT 06106, USA.

DOI: 10.2217/fca.10.6

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MeSH Terms: Anticoagulants, Aryl Hydrocarbon Hydroxylases, Clopidogrel, Cost-Benefit Analysis, Cytochrome P-450 CYP2C19, Cytochrome P-450 CYP2C9, Cytochrome P-450 Enzyme System, Cytochrome P450 Family 4, Dose-Response Relationship, Drug, Genetic Privacy, Genotype, Health Policy, Humans, Mixed Function Oxygenases, Pharmacogenetics, Piperazines, Platelet Aggregation Inhibitors, Polymorphism, Single Nucleotide, Prasugrel Hydrochloride, Precision Medicine, Purinergic P2 Receptor Antagonists, Thiophenes, Ticlopidine, Vitamin K Epoxide Reductases, Warfarin