Cost-effectiveness of using pharmacogenetic information in warfarin dosing for patients with nonvalvular atrial fibrillation

Mark H. Eckman, Jonathan Rosand, Steven M. Greenberg, Brian F. Gage

Research output: Contribution to journalArticlepeer-review

242 Scopus citations

Abstract

Background: Variants in genes involved in warfarin metabolism and sensitivity affect individual warfarin requirements and the risk for bleeding. Testing for these variant alleles might allow more personalized dosing of warfarin during the induction phase. In 2007, the U.S. Food and Drug Administration changed the labeling for warfarin (Coumadin, Bristol-Myers Squibb, Princeton, New Jersey), suggesting that clinicians consider genetic testing before initiating therapy. Objective: To examine the cost-effectiveness of genotype-guided dosing versus standard induction of warfarin therapy for patients with nonvalvular atrial fibrillation. Design: Markov state transition decision model. Data Sources: MEDLINE searches and bibliographies from relevant articles of literature published in English. Target Population: Outpatients or inpatients requiring initiation of warfarin therapy. The base case was a man age 69 years with newly diagnosed nonvalvular atrial fibrillation and no contraindications to warfarin therapy. Time Horizon: Lifetime. Perspective: Societal. Intervention: Genotype-guided dosing consisting of genotyping for CYP2C9*2, CYP2C9*3, and/or VKORC1 versus standard warfarin induction. Outcome Measures: Effectiveness was measured in quality-adjusted life-years (QALYs), and costs were in 2007 U.S. dollars. Results: In the base case, genotype-guided dosing resulted in better outcomes, but at a relatively high cost. Overall, the marginal cost-effectiveness of testing exceeded $170 000 per QALY. On the basis of current data and cost of testing (about $400), there is only a 10% chance that genotype-guided dosing is likely to be cost-effective (that is, <$50 000 per QALY). Sensitivity analyses revealed that for genetic testing to cost less than $50 000 per QALY, it would have to be restricted to patients at high risk for hemorrhage or meet the following optimistic criteria: prevent greater than 32% of major bleeding events, be available within 24 hours, and cost less than $200. Limitation: Few published studies describe the effect of genotype-guided dosing on major bleeding events, and although these studies show a trend toward decreased bleeding, the results are not statistically significant. Conclusion: Warfarin-related genotyping is unlikely to be cost-effective for typical patients with nonvalvular atrial fibrillation, but may be cost-effective in patients at high risk for hemorrhage who are starting warfarin therapy. Funding: The National Institute of Diabetes and Digestive and Kidney Diseases; National Heart, Lung, and Blood Institute; Foundation for Informed Medical Decision Making; National Institutes of Neurological Disorders and Stroke; Deane Institute for Integrative Study of Atrial Fibrillation and Stroke; and American Heart Association.

Original languageEnglish
Pages (from-to)73-83
Number of pages11
JournalAnnals of internal medicine
Volume150
Issue number2
DOIs
StatePublished - Jan 20 2009

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