title: Long-term anticoagulant effects of the CYP2C9 and VKORC1 genotypes in acenocoumarol users.
abstract: BACKGROUND
  The required acenocoumarol dose and the risk of underanticoagulation and overanticoagulation are associated with the CYP2C9 and VKORC1 genotypes. However, the duration of the effects of these genes on anticoagulation is not yet known.
  
  
  OBJECTIVE
  In the present study, the effects of these polymorphisms on the risk of underanticoagulation and overanticoagulation over time after the start of acenocoumarol were investigated.
  
  
  METHODS
  In three cohorts, we analyzed the relationship between the CYP2C9 and VKORC1 genotypes and the incidence of subtherapeutic or supratherapeutic International Normalized Ratio (INR) values (< 2 and > 3.5) or severe overanticoagulation (INR > 6) for different time periods after treatment initiation.
  
  
  RESULTS
  Patients with polymorphisms in CYP2C9 and VKORC1 had a higher risk of overanticoagulation (up to 74%) and a lower risk of underanticoagulation (down to 45%) in the first month of treatment with acenocoumarol, but this effect diminished after 1-6 months.
  
  
  CONCLUSIONS
  Knowledge of the patient's genotype therefore might assist physicians to adjust doses in the first month(s) of therapy.
authors.affiliation: Division of Pharmacoepidemiology and Clinical Pharmacology, Utrecht Institute of Pharmaceutical Sciuences, Utrecht University, Utrecht, the Netherlands.
authors.forename: T I
authors.initials: TI
authors.lastname: Verhoef
authors.forename: W K
authors.initials: WK
authors.lastname: Redekop
authors.forename: M M
authors.initials: MM
authors.lastname: Buikema
authors.forename: T
authors.initials: T
authors.lastname: Schalekamp
authors.forename: F J M
authors.initials: FJ
authors.lastname: Van Der Meer
authors.forename: S
authors.initials: S
authors.lastname: Le Cessie
authors.forename: J A M
authors.initials: JA
authors.lastname: Wessels
authors.forename: R M F
authors.initials: RM
authors.lastname: Van Schie
authors.forename: A
authors.initials: A
authors.lastname: De Boer
authors.forename: M
authors.initials: M
authors.lastname: Teichert
authors.forename: L E
authors.initials: LE
authors.lastname: Visser
authors.forename: A H
authors.initials: AH
authors.lastname: Maitland-Van Der Zee
mesh_terms: D000074:Acenocoumarol / Q000008:administration & dosage / Q000009:adverse effects / Q000493:pharmacokinetics*; D000368:Aged; D000925:Anticoagulants / Q000008:administration & dosage / Q000009:adverse effects / Q000493:pharmacokinetics*; D001189:Aryl Hydrocarbon Hydroxylases / Q000235:genetics* / Q000378:metabolism; D001777:Blood Coagulation / Q000187:drug effects*; D065729:Cytochrome P-450 CYP2C9; D004334:Drug Administration Schedule; D054796:Drug Dosage Calculations; D016903:Drug Monitoring / Q000379:methods; D005260:Female; D005787:Gene Frequency; D005838:Genotype; D006801:Humans; D019934:International Normalized Ratio; D008297:Male; D008508:Medication Errors / Q000517:prevention & control; D006899:Mixed Function Oxygenases / Q000235:genetics* / Q000378:metabolism; D009426:Netherlands; D010597:Pharmacogenetics; D010641:Phenotype; D011110:Polymorphism, Genetic; D011237:Predictive Value of Tests; D018570:Risk Assessment; D012307:Risk Factors; D013997:Time Factors; D064417:Vitamin K Epoxide Reductases
chemical_list: D000925:Anticoagulants; D006899:Mixed Function Oxygenases; C450260:CYP2C9 protein, human; D065729:Cytochrome P-450 CYP2C9; D001189:Aryl Hydrocarbon Hydroxylases; C578523:VKORC1 protein, human; D064417:Vitamin K Epoxide Reductases; D000074:Acenocoumarol