title: Cost-effectiveness of genotype-guided warfarin therapy for anticoagulation in elderly patients with atrial fibrillation.
abstract: BACKGROUND
  In patients with atrial fibrillation (AF), anticoagulation with warfarin decreases the risk of embolic stroke by >50%. Identification of genetic polymorphisms in enzymes involved in the metabolism of warfarin can partially predict the maintenance dose and thus potentially decrease the incidence of bleeding episodes secondary to warfarin overdose.
  
  
  OBJECTIVE
  The objectives of this study were to evaluate the potential clinical and economic outcomes of genotype-guided warfarin therapy in elderly patients newly diagnosed with AF and to identify a threshold in bleeding risk at which such therapy may be cost-effective.
  
  
  METHODS
  A decision tree was designed to represent the medical decision (pharmacogenetic testing or not) and the main clinical outcomes (embolic stroke, bleeding). Event rates of embolic stroke and bleeding complications were based on data from previously published clinical trials and an observational study, respectively; costs were from a third-party payer perspective; and utilities were from the patient perspective. It was assumed that use of pharma-cogenetic testing would not lead the clinician to make any potentially harmful modifications to the regimen.
  
  
  RESULTS
  This analysis found that any reduction in major bleeding as a result of pharmacogenetic testing would lead to improved utility. The higher costs of pharmacogenetic testing compared with no testing would be immediately offset by any reduction in major bleeding.
  
  
  CONCLUSIONS
  In this decision analysis, genotype-guided warfarin therapy for anticoagulation in elderly patients with AF was potentially cost-effective, and its benefits were closely related to efficacy in preventing bleeding events. Clinical trials testing the efficacy of genotype-guided warfarin therapy are warranted.
authors.affiliation: Division of Endocrinology, Metabolism, and Lipid Research, Washington University School of Medicine, St. Louis, Missouri 63110, USA.
authors.forename: Julio A
authors.initials: JA
authors.lastname: Leey
authors.forename: Steve
authors.initials: S
authors.lastname: McCabe
authors.forename: Jennifer A
authors.initials: JA
authors.lastname: Koch
authors.forename: Toni P
authors.initials: TP
authors.lastname: Miles
mesh_terms: D000368:Aged; D000925:Anticoagulants / Q000009:adverse effects / Q000191:economics* / Q000627:therapeutic use*; D001281:Atrial Fibrillation / Q000188:drug therapy* / Q000191:economics / Q000235:genetics*; D003362:Cost-Benefit Analysis; D005838:Genotype; D006470:Hemorrhage / Q000139:chemically induced / Q000191:economics / Q000453:epidemiology; D006801:Humans; D019934:International Normalized Ratio; D020766:Intracranial Embolism / Q000191:economics / Q000453:epidemiology / Q000517:prevention & control; D010597:Pharmacogenetics; D018570:Risk Assessment; D020521:Stroke / Q000191:economics / Q000453:epidemiology / Q000517:prevention & control; D016896:Treatment Outcome; D014859:Warfarin / Q000009:adverse effects / Q000191:economics* / Q000627:therapeutic use*
chemical_list: D000925:Anticoagulants; D014859:Warfarin