Cost-Effectiveness of Using Pharmacogenetic Information in Warfarin Dosing for Patients With Nonvalvular Atrial Fibrillation

被引:215
作者
Eckman, Mark H. [1 ]
Rosand, Jonathan
Greenberg, Steven M.
Gage, Brian F.
机构
[1] Univ Cincinnati, Med Ctr, Cincinnati, OH 45267 USA
关键词
ORAL ANTICOAGULANT TREATMENT; QUALITY-OF-LIFE; BLEEDING COMPLICATIONS; ORTHOPEDIC PATIENTS; RISK-FACTORS; INTRACEREBRAL HEMORRHAGE; INTRACRANIAL HEMORRHAGE; ANTITHROMBOTIC THERAPY; CYTOCHROME-P450; CYP2C9; DECISION-ANALYSIS;
D O I
10.7326/0003-4819-150-2-200901200-00005
中图分类号
R5 [内科学];
学科分类号
1002 ; 100201 ;
摘要
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.
引用
收藏
页码:73 / U31
页数:14
相关论文
共 76 条
[61]   Genetic determinants of response to warfarin during initial anticoagulation [J].
Schwarz, Ute I. ;
Ritchie, Marylyn D. ;
Bradford, Yuki ;
Li, Chun ;
Dudek, Scott M. ;
Frye-Anderson, Amy ;
Kim, Richard B. ;
Roden, Dan M. ;
Stein, C. Michael .
NEW ENGLAND JOURNAL OF MEDICINE, 2008, 358 (10) :999-1008
[62]   Genetic analysis of the human cytochrome P450 CYP2C9 locus [J].
Stubbins, MJ ;
Harries, LW ;
Smith, G ;
Tarbit, MH ;
Wolf, CR .
PHARMACOGENETICS, 1996, 6 (05) :429-439
[63]   Influence of cytochrome P-450CYP2C9 polymorphisms on warfarin sensitivity and risk of over-anticoagulation in patients on long-term treatment [J].
Taube, J ;
Halsall, D ;
Baglin, T .
BLOOD, 2000, 96 (05) :1816-1819
[64]   Health-related quality of life after stroke - A comprehensive review [J].
Tengs, TO ;
Yu, M ;
Luistro, E .
STROKE, 2001, 32 (04) :964-971
[65]  
*U PENNS SCH MED N, GEN GUID DOS WARF CL
[66]  
*UD NAT I HLTH, PHARM STUD WARF DOS
[67]  
*US DEP LAB BUR LA, CONS PRIC INC ARCH C
[68]  
*US FDA, FDA APPR UPD WARF CO
[69]   The risk of bleeding complications in patients with cytochrome P450CYP2C9*2 or CYP2C9*3 alleles on acenocoumarol or phenprocoumon [J].
Visser, LE ;
van Schaik, RHN ;
van Vliet, M ;
Trienekens, PH ;
De Smet, PAGM ;
Vulto, AG ;
Hofman, A ;
van Duijn, CM ;
Stricker, BHC .
THROMBOSIS AND HAEMOSTASIS, 2004, 92 (01) :61-66
[70]   Prospective dosing of warfarin based on cytochrome P-4502C9 genotype [J].
Voora, D ;
Eby, C ;
Linder, MW ;
Milligan, PE ;
Bukaveckas, BL ;
McLeod, HL ;
Maloney, W ;
Clohisy, J ;
Burnett, RS ;
Grosso, L ;
Gatchel, SK ;
Gage, BF .
THROMBOSIS AND HAEMOSTASIS, 2005, 93 (04) :700-705