title: Cost-effectiveness of genotype-guided warfarin dosing for patients with atrial fibrillation.
abstract: BACKGROUND
  CYP2C9 and VKORC1 genotyping has been advocated as a means of improving the accuracy of warfarin dosing. However, the effectiveness of genotyping in improving anticoagulation control and reducing major bleeding has not yet been compellingly demonstrated. Genotyping currently costs $400 to $550.
  
  
  RESULTS
  We constructed a Markov model to evaluate whether and under what circumstances genetically-guided warfarin dosing could be cost-effective for newly diagnosed atrial fibrillation patients. Estimates of clinical event rates, treatment and adverse event costs, and utilities for health states were derived from the published literature. The cost-effectiveness of genetically-guided dosing was highly dependent on the assumed effectiveness of genotyping in increasing the amount of time patients spend appropriately anticoagulated. If genotyping increases the time spent in the target international normalized ratio range by <5 percentage points, its incremental cost-effectiveness ratio would be greater than $100,000 per quality-adjusted life year. The incremental cost-effectiveness ratio falls below $50,000 per quality-adjusted life year if genotyping increases the time spent in range by 9 percentage points. The results were also sensitive to assumptions about the rate of major bleeding events during treatment initiation and the cost of the test.
  
  
  CONCLUSIONS
  Our results suggest that genotyping before warfarin initiation will be cost-effective for patients with atrial fibrillation only if it reduces out-of-range international normalized ratio values by more than 5 to 9 percentage points compared with usual care. Given the current uncertainty surrounding genotyping efficacy, caution should be taken in advocating the widespread adoption of this strategy.
authors.affiliation: Division of Pharmacoepidemiology and Pharmacoeconomics, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA 02120, USA. arpatrick@partners.org
authors.forename: Amanda R
authors.initials: AR
authors.lastname: Patrick
authors.forename: Jerry
authors.initials: J
authors.lastname: Avorn
authors.forename: Niteesh K
authors.initials: NK
authors.lastname: Choudhry
mesh_terms: D000368:Aged; D000925:Anticoagulants / Q000008:administration & dosage* / Q000009:adverse effects / Q000191:economics*; D001189:Aryl Hydrocarbon Hydroxylases / Q000235:genetics; D001281:Atrial Fibrillation / Q000188:drug therapy* / Q000191:economics* / Q000235:genetics / Q000401:mortality; D002545:Brain Ischemia / Q000453:epidemiology; D003362:Cost-Benefit Analysis; D065729:Cytochrome P-450 CYP2C9; D016527:Drug Costs; D005820:Genetic Testing / Q000191:economics; D005838:Genotype; D006470:Hemorrhage / Q000139:chemically induced / Q000453:epidemiology; D006801:Humans; D015994:Incidence; D008390:Markov Chains; D006899:Mixed Function Oxygenases / Q000235:genetics; D017059:Models, Econometric; D057285:Precision Medicine / Q000191:economics; D011788:Quality of Life; D020521:Stroke / Q000453:epidemiology; D064417:Vitamin K Epoxide Reductases; D014859:Warfarin / Q000008:administration & dosage* / Q000009:adverse effects / Q000191:economics*
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