Genotype-guided coumarin dosing: where are we now and where do we need to go next?

Abstract

Introduction: A large proportion of the coumarin dose variability is explained by environmental factors and by common genetic variants in the VKORC1 and CYP2C9 genes. Genotype-guided coumarin dosing has been proposed for a more accurate prediction of the coumarin dose in order to reduce the incidence of coumarin-related complications.

Areas covered: This review discusses the current state of coumarin pharmacogenetics, the evidence from recent randomized controlled trials and economic evaluations regarding the possible clinical implementation of genotype-guided coumarin dosing.

Expert opinion: When the VKORC1 and CYP2C9 genotypes are available before the start of coumarin therapy in individuals of European ancestry, a genetic-guided algorithm should be used for dose determination. Ethnicity-specific pharmacogenetic algorithms should be tested in other populations. At this moment the evidence is not sufficient to support genotyping before coumarin therapy initiation. Based on results from recent randomized controlled trials, a clinical dosing algorithm could be considered in the initial phase of coumarin treatment. Current economic studies indicate that genotype-guided dosing could be cost-effective, but the clinical implementation of genetic-guided coumarin therapy will depend on the cost of pharmacogenetic tests and the availability of novel oral anticoagulants.

Keywords:

• coumarins
• CYP2C9
• dose
• genetic-guided
• pharmacogenetics
• polymorphism
• VKORC1
• warfarin

Acknowledgements

FW Asselbergs is supported by a Dekker scholarship-Junior Staff Member 2014T001 – Netherlands Heart Foundation.

Declaration of interest

The authors have no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.

Notes

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