title: Genotype-guided coumarin dosing: where are we now and where do we need to go next?
abstract: BACKGROUND
  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.
  
  
  METHODS
  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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Utrecht University, Division of Pharmacoepidemiology and Clinical Pharmacology, Department of Pharmaceutical Sciences , PO Box 80 082, 3508 TB Utrecht , The Netherlands +31 0 6 22736715 ; +31 0 30 2539166 ; a.h.maitland@uu.nl.
authors.forename: Ekaterina V
authors.initials: EV
authors.lastname: Baranova
authors.forename: Talitha I
authors.initials: TI
authors.lastname: Verhoef
authors.forename: Folkert W
authors.initials: FW
authors.lastname: Asselbergs
authors.forename: Anthonius
authors.initials: A
authors.lastname: de Boer
authors.forename: Anke-Hilse
authors.initials: AH
authors.lastname: Maitland-van der Zee
mesh_terms: D000465:Algorithms; D000925:Anticoagulants / Q000008:administration & dosage*; D003374:Coumarins / Q000008:administration & dosage*; D065729:Cytochrome P-450 CYP2C9 / Q000235:genetics*; D004305:Dose-Response Relationship, Drug; D005006:Ethnicity / Q000235:genetics; D014644:Genetic Variation; D005838:Genotype; D006801:Humans; D010597:Pharmacogenetics; D064417:Vitamin K Epoxide Reductases / Q000235:genetics*
chemical_list: D000925:Anticoagulants; D003374:Coumarins; C450260:CYP2C9 protein, human; D065729:Cytochrome P-450 CYP2C9; C578523:VKORC1 protein, human; D064417:Vitamin K Epoxide Reductases
keywords: CYP2C9; VKORC1; coumarins; dose; genetic-guided; pharmacogenetics; polymorphism; warfarin