title: Warfarin genotyping reduces hospitalization rates results from the MM-WES (Medco-Mayo Warfarin Effectiveness study).
abstract: OBJECTIVE
  This study was designed to determine whether genotype testing for patients initiating warfarin treatment will reduce the incidence of hospitalizations, including those due to bleeding or thromboembolism.
  
  
  BACKGROUND
  Genotypic variations in CYP2C9 and VKORC1 have been shown to predict warfarin dosing, but no large-scale studies have prospectively evaluated the clinical effectiveness of genotyping in naturalistic settings across the U.S.
  
  
  METHODS
  This national, prospective, comparative effectiveness study compared the 6-month incidence of hospitalization in patients receiving warfarin genotyping (n = 896) versus a matched historical control group (n = 2,688). To evaluate for temporal changes in the outcomes of warfarin treatment, a secondary analysis compared outcomes for 2 external control groups drawn from the same 2 time periods.
  
  
  RESULTS
  Compared with the historical control group, the genotyped cohort had 31% fewer hospitalizations overall (adjusted hazard ratio [HR]: 0.69, 95% confidence interval [CI]: 0.58 to 0.82, p < 0.001) and 28% fewer hospitalizations for bleeding or thromboembolism (HR: 0.72, 95% CI: 0.53 to 0.97, p = 0.029) during the 6-month follow-up period. Findings from a per-protocol analysis were even stronger: 33% lower risk of all-cause hospitalization (HR: 0.67, 95% CI: 0.55 to 0.81, p < 0.001) and 43% lower risk of hospitalization for bleeding or thromboembolism (HR: 0.57, 95% CI: 0.39 to 0.83, p = 0.003) in patients who were genotyped. During the same period, there was no difference in outcomes between the 2 external control groups.
  
  
  CONCLUSIONS
  Warfarin genotyping reduced the risk of hospitalization in outpatients initiating warfarin. (The Clinical and Economic Impact of Pharmacogenomic Testing of Warfarin Therapy in Typical Community Practice Settings [MHSMayoWarf1]; NCT00830570).
authors.affiliation: Department of Medical and Analytical Affairs, Medco Health Solutions, Inc., Franklin Lakes, New Jersey 07417, USA. Robert_Epstein@medco.com
authors.forename: Robert S
authors.initials: RS
authors.lastname: Epstein
authors.forename: Thomas P
authors.initials: TP
authors.lastname: Moyer
authors.forename: Ronald E
authors.initials: RE
authors.lastname: Aubert
authors.forename: Dennis J
authors.initials: DJ
authors.lastname: O Kane
authors.forename: Fang
authors.initials: F
authors.lastname: Xia
authors.forename: Robert R
authors.initials: RR
authors.lastname: Verbrugge
authors.forename: Brian F
authors.initials: BF
authors.lastname: Gage
authors.forename: J Russell
authors.initials: JR
authors.lastname: Teagarden
mesh_terms: D000368:Aged; D000925:Anticoagulants / Q000009:adverse effects* / Q000627:therapeutic use; D001189:Aryl Hydrocarbon Hydroxylases / Q000235:genetics; D016022:Case-Control Studies; D016001:Confidence Intervals; D065729:Cytochrome P-450 CYP2C9; D004305:Dose-Response Relationship, Drug; D004334:Drug Administration Schedule; D005260:Female; D005838:Genotype; D006470:Hemorrhage / Q000139:chemically induced / Q000235:genetics* / Q000401:mortality; D006760:Hospitalization / Q000706:statistics & numerical data*; D006801:Humans; D015994:Incidence; D008297:Male; D008875:Middle Aged; D006899:Mixed Function Oxygenases / Q000235:genetics; D010597:Pharmacogenetics; D011336:Probability; D016016:Proportional Hazards Models; D018570:Risk Assessment; D016019:Survival Analysis; D013923:Thromboembolism / Q000139:chemically induced / Q000235:genetics* / Q000401:mortality; D016896:Treatment Outcome; D064417:Vitamin K Epoxide Reductases; D014859:Warfarin / Q000009:adverse effects* / Q000627:therapeutic use
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