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: DESIGN: Markov state transition decision model. DATA SOURCES: MEDLINE searches and bibliographies from relevant articles of literature published in English. TARGET POPULATION: 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:
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Authors | Mark H Eckman, Jonathan Rosand, Steven M Greenberg, Brian F Gage |
Journal | Annals of internal medicine
(Ann Intern Med)
Vol. 150
Issue 2
Pg. 73-83
(Jan 20 2009)
ISSN: 1539-3704 [Electronic] United States |
PMID | 19153410
(Publication Type: Case Reports, Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)
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Chemical References |
- Anticoagulants
- Warfarin
- Mixed Function Oxygenases
- CYP2C9 protein, human
- Cytochrome P-450 CYP2C9
- Aryl Hydrocarbon Hydroxylases
- VKORC1 protein, human
- Vitamin K Epoxide Reductases
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Topics |
- Aged
- Anticoagulants
(administration & dosage, adverse effects)
- Aryl Hydrocarbon Hydroxylases
(genetics)
- Atrial Fibrillation
(drug therapy, genetics)
- Cost-Benefit Analysis
- Cytochrome P-450 CYP2C9
- Decision Support Techniques
- Genotype
- Hemorrhage
(chemically induced)
- Humans
- Male
- Markov Chains
- Mixed Function Oxygenases
(genetics)
- Quality-Adjusted Life Years
- Sensitivity and Specificity
- Vitamin K Epoxide Reductases
- Warfarin
(administration & dosage, adverse effects)
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