title: A pharmacogenetic versus a clinical algorithm for warfarin dosing.
abstract: BACKGROUND
  The clinical utility of genotype-guided (pharmacogenetically based) dosing of warfarin has been tested only in small clinical trials or observational studies, with equivocal results.
  
  
  METHODS
  We randomly assigned 1015 patients to receive doses of warfarin during the first 5 days of therapy that were determined according to a dosing algorithm that included both clinical variables and genotype data or to one that included clinical variables only. All patients and clinicians were unaware of the dose of warfarin during the first 4 weeks of therapy. The primary outcome was the percentage of time that the international normalized ratio (INR) was in the therapeutic range from day 4 or 5 through day 28 of therapy.
  
  
  RESULTS
  At 4 weeks, the mean percentage of time in the therapeutic range was 45.2% in the genotype-guided group and 45.4% in the clinically guided group (adjusted mean difference, [genotype-guided group minus clinically guided group], -0.2; 95% confidence interval, -3.4 to 3.1; P=0.91). There also was no significant between-group difference among patients with a predicted dose difference between the two algorithms of 1 mg per day or more. There was, however, a significant interaction between dosing strategy and race (P=0.003). Among black patients, the mean percentage of time in the therapeutic range was less in the genotype-guided group than in the clinically guided group. The rates of the combined outcome of any INR of 4 or more, major bleeding, or thromboembolism did not differ significantly according to dosing strategy.
  
  
  CONCLUSIONS
  Genotype-guided dosing of warfarin did not improve anticoagulation control during the first 4 weeks of therapy. (Funded by the National Heart, Lung, and Blood Institute and others; COAG ClinicalTrials.gov number, NCT00839657.).
authors.affiliation: The authors' affiliations are listed in the Appendix.
authors.forename: Stephen E
authors.initials: SE
authors.lastname: Kimmel
authors.forename: Benjamin
authors.initials: B
authors.lastname: French
authors.forename: Scott E
authors.initials: SE
authors.lastname: Kasner
authors.forename: Julie A
authors.initials: JA
authors.lastname: Johnson
authors.forename: Jeffrey L
authors.initials: JL
authors.lastname: Anderson
authors.forename: Brian F
authors.initials: BF
authors.lastname: Gage
authors.forename: Yves D
authors.initials: YD
authors.lastname: Rosenberg
authors.forename: Charles S
authors.initials: CS
authors.lastname: Eby
authors.forename: Rosemary A
authors.initials: RA
authors.lastname: Madigan
authors.forename: Robert B
authors.initials: RB
authors.lastname: McBane
authors.forename: Sherif Z
authors.initials: SZ
authors.lastname: Abdel-Rahman
authors.forename: Scott M
authors.initials: SM
authors.lastname: Stevens
authors.forename: Steven
authors.initials: S
authors.lastname: Yale
authors.forename: Emile R
authors.initials: ER
authors.lastname: Mohler
authors.forename: Margaret C
authors.initials: MC
authors.lastname: Fang
authors.forename: Vinay
authors.initials: V
authors.lastname: Shah
authors.forename: Richard B
authors.initials: RB
authors.lastname: Horenstein
authors.forename: Nita A
authors.initials: NA
authors.lastname: Limdi
authors.forename: James A S
authors.initials: JA
authors.lastname: Muldowney
authors.forename: Jaspal
authors.initials: J
authors.lastname: Gujral
authors.forename: Patrice
authors.initials: P
authors.lastname: Delafontaine
authors.forename: Robert J
authors.initials: RJ
authors.lastname: Desnick
authors.forename: Thomas L
authors.initials: TL
authors.lastname: Ortel
authors.forename: Henny H
authors.initials: HH
authors.lastname: Billett
authors.forename: Robert C
authors.initials: RC
authors.lastname: Pendleton
authors.forename: Nancy L
authors.initials: NL
authors.lastname: Geller
authors.forename: Jonathan L
authors.initials: JL
authors.lastname: Halperin
authors.forename: Samuel Z
authors.initials: SZ
authors.lastname: Goldhaber
authors.forename: Michael D
authors.initials: MD
authors.lastname: Caldwell
authors.forename: Robert M
authors.initials: RM
authors.lastname: Califf
authors.forename: Jonas H
authors.initials: JH
authors.lastname: Ellenberg
mesh_terms: D000328:Adult; D000368:Aged; D000465:Algorithms; D000925:Anticoagulants / Q000008:administration & dosage* / Q000009:adverse effects; D001189:Aryl Hydrocarbon Hydroxylases / Q000235:genetics*; D065729:Cytochrome P-450 CYP2C9; D004311:Double-Blind Method; D005260:Female; D005500:Follow-Up Studies; D005838:Genotype; D006470:Hemorrhage / Q000139:chemically induced; D006801:Humans; D019934:International Normalized Ratio; D008297:Male; D010597:Pharmacogenetics; D013923:Thromboembolism; D017211:Treatment Failure; D064417:Vitamin K Epoxide Reductases / Q000235:genetics*; D014859:Warfarin / Q000008:administration & dosage* / Q000009:adverse effects
chemical_list: D000925:Anticoagulants; D014859:Warfarin; C450260:CYP2C9 protein, human; D065729:Cytochrome P-450 CYP2C9; D001189:Aryl Hydrocarbon Hydroxylases; C578523:VKORC1 protein, human; D064417:Vitamin K Epoxide Reductases