title: The combined effects of clinical factors and CYP2C9 and VKORC1 gene polymorphisms on initiating warfarin treatment in patients after cardiac valve surgery.
abstract: OBJECTIVE
  Recent studies have shown that, after heart valve surgery, patients may require a more precise warfarin dosage than their non-surgical counterparts. The study aim was to analyze the influence of certain clinical factors and CYP2C9 and VKORC1 gene polymorphisms on the efficacy of initiation of warfarin treatment in patients after cardiac valve surgery.
  
  
  METHODS
  Following heart valve surgery, a total of 185 patients was genotyped for the CYP2C9*1, *2, *3 alleles and for VKORC1 (G-1639A) gene promoter polymorphism.
  
  
  RESULTS
  A hierarchical stepwise multivariate linear regression model was used to evaluate factors affecting the optimal warfarin dosage. Patient age and body weight, together with hepatic malfunction in the cohort population, accounted for 12% of the variation in warfarin dosage (R2 = 0.119). The introduction of concomitant medications, more than doubled (R2 = 0.316) the accuracy of the dosage algorithm. Medications such as cephalosporin, amiodarone, loop diuretics, ibuprofen or diclofenac, omeprazole and beta-blockers had significant effects on the warfarin daily dosage in this model. However, the greatest accuracy was obtained when the patient's CYP2C9 and VKORC1 genotype was introduced into the formula as the critical factor (R2 = 0.429).
  
  
  CONCLUSIONS
  The study results suggested that, after cardiac valve surgery, by combining the clinical, genetic and anthropometric data of a patient, the warfarin dose may be estimated to 43% accuracy at the initiation of anticoagulant therapy.
authors.affiliation: Institute of Cardiology of Medical Academy of Lithuanian University of Health Sciences, Kaunas, Lithuania. vacis_tatarunas@takas.lt
authors.forename: Vacis
authors.initials: V
authors.lastname: Tatarūnas
authors.forename: Vaiva
authors.initials: V
authors.lastname: Lesauskaite
authors.forename: Audrone
authors.initials: A
authors.lastname: Veikutiene
authors.forename: Pranas
authors.initials: P
authors.lastname: Grybauskas
authors.forename: Povilas
authors.initials: P
authors.lastname: Jakuska
authors.forename: Rimantas
authors.initials: R
authors.lastname: Benetis
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000465:Algorithms; D000925:Anticoagulants / Q000008:administration & dosage*; D001189:Aryl Hydrocarbon Hydroxylases / Q000235:genetics*; D065729:Cytochrome P-450 CYP2C9; D005260:Female; D019918:Heart Valve Prosthesis Implantation; D006801:Humans; D016014:Linear Models; D008297:Male; D008875:Middle Aged; D006899:Mixed Function Oxygenases / Q000235:genetics*; D011110:Polymorphism, Genetic; D011182:Postoperative Care; D064417:Vitamin K Epoxide Reductases; D014859:Warfarin / Q000008:administration & dosage*; D055815:Young Adult
chemical_list: D000925:Anticoagulants; D014859:Warfarin; 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