RSS Feeds
Cost-Effectiveness of Using Pharmacogenetic Information in Warfarin Dosing for Patients With Nonvalvular Atrial Fibrillation
- Mark H. Eckman, MD, MS;
- Jonathan Rosand, MD, MSc;
- Steven M. Greenberg, MD, PhD; and
- Brian F. Gage, MD, MSc
- From the University of Cincinnati, Cincinnati, Ohio; Massachusetts General Hospital, Boston, Massachusetts; and Washington University in St. Louis, St. Louis, Missouri.
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.
Article and Author Information
-
Grant Support: By National Institute of Diabetes and Digestive and Kidney Diseases grant K23 DK075599, National Heart, Lung, and Blood Institute grant K30 HL078581-01, and the Foundation for Informed Medical Decision Making (Dr. Eckman); National Institutes of Neurological Disorders and Stroke grants K23 NS42695-01 and R01 NS04217 and the Deane Institute for Integrative Study of Atrial Fibrillation and Stroke (Dr. Rosand); National Institutes of Neurological Disorders and Stroke grant R01 NS04217 (Dr. Greenberg); and the Established Investigator Award from the American Heart Association (Dr. Gage).
-
Potential Financial Conflicts of Interest: Consultancies: B.F. Gage (Bristol-Myers Squibb), Grants received: B.F. Gage (Osmetech).
-
Reproducible Research Statement: Study protocol and data set: Not available. Statistical code: The decision model is available from Dr. Eckman (e-mail, mark.eckman{at}uc.edu).
-
Requests for Single Reprints: Mark H. Eckman, MD, MS, University of Cincinnati Medical Center, PO Box 670535, Cincinnati, OH 45267-0535; e-mail, mark.eckman{at}uc.edu.
-
Current Author Addresses: Dr. Eckman: University of Cincinnati Medical Center, PO Box 670535, Cincinnati, OH 45267-0535.
-
Dr. Rosand: Center for Human Genetic Research, Richard B. Simches Research Center, Massachusetts General Hospital, CPZN-6810, 185 Cambridge Street, Boston, MA 02114.
-
Dr. Greenberg: Massachusetts General Hospital, 175 Cambridge Street, Suite 300, Boston, MA 02114
-
Dr. Gage: Washington University, 660 South Euclid Avenue, Suite CB8005, St. Louis, MO 63110.
-
Author Contributions: Conception and design: M.H. Eckman,
-
Analysis and interpretation of the data: M.H. Eckman, B.F. Gage.
-
Drafting of the article: M.H. Eckman.
-
Critical revision of the article for important intellectual content: M.H. Eckman, J. Rosand, S.M. Greenberg, B.F. Gage.
-
Final approval of the article: M.H. Eckman, J. Rosand, S.M. Greenberg, B.F. Gage.
-
Statistical expertise: M.H. Eckman, B.F. Gage.
-
Collection and assembly of data: M.H. Eckman.
Related Clinical Content
