Genotype-Guided Warfarin Dosing: Is It Cost-Effective? [Новость добавлена - 11.02.2009]

Costs would be above societys willingness-to-pay threshold unless the approach could prevent at least a third of bleeding events in patients with nonvalvular atrial fibrillation.

The considerable variation in patient sensitivity to warfarin is attributed
in part to mutations in genes that govern metabolism of this anticoagulant
agent and its target, vitamin K epoxide reductase (JW Oncol Hematol Apr 1
2008). One third of this variation in sensitivity arises from mutations in
two genes: CYP2C9 (which encodes cytochrome P450:2C9) and VKORC1 (which
encodes vitamin K epoxide reductase C1). Individuals with CYP2C9 mutations
have diminished ability to metabolize warfarin, and those with VKORC1 group
A haplotype have excess sensitivity to warfarin-induced inhibition.
Heightened warfarin sensitivity is associated with greater difficulty in
maintaining prothrombin times within the therapeutic range and with excess
risk for bleeding. As a result, the FDA recently suggested that warfarin
labeling should urge clinicians to consider genotyping patients before
initiating warfarin therapy. However, concerns about the effectiveness and
cost of this approach have been raised.

To determine whether genotyping of patients who start warfarin therapy
would be cost-effective, investigators performed a meta-analysis of three
studies of genotype-based warfarin dosing versus standard
warfarin-induction therapy that collectively involved more than 400
patients with nonvalvular atrial fibrillation. The authors assumed that
genotype-guided dosing would lower rates of hemorrhagic events by 32%
(calculated using data from the studies); benefits would be confined to the
first month of therapy (the point at which most patients reach their
maintenance doses); genotyping would be performed by independent clinical
laboratories at a cost of US$400 per test; and results could be ready in 3
days. Based on these assumptions, the marginal cost-effectiveness ratio of
genotype-guided dosing exceeded $170,000 per quality-adjusted life-year
(QALY), far more than the generally accepted limit of $50,000 per QALY that
society is willing to pay for medical therapy.

The authors also considered a rosier scenario in which genotyping could be
performed in-hospital for $200 per test and results could be ready in 1
day, thus enabling more-rapid initiation of therapy. However, even with
these assumptions, the marginal cost of testing would be $51,000 per QALY.
The cost would fall below $50,000 per QALY in this more optimistic scenario
only if genotype-guided dosing were to decrease hemorrhagic events by more
than 32%.

Comment: Perhaps the most important consideration in this analysis is
whether genotyping can have a major impact on prevention of
life-threatening hemorrhage. The authors showed that a 32% reduction in
bleeding was achieved when genotype-guided warfarin dosing was implemented.
However, the confidence intervals were broad, and the drop in likelihood of
bleeding was not significant. To realize the most cost-effective use of
genotyping, the authors suggest selecting patients at high risk for
bleeding, such as those with hepatic or renal disease, histories of ethanol
abuse, malignancy, age >75, reduced platelet count or function,
uncontrolled hypertension, anemia, fall risk, or stroke (features included
in the HEMMOR{sub 2}HAGES score; Am Heart J 2006; 151:713).

-- David Green, MD, PhD

Published in Journal Watch Oncology and Hematology February 10, 2009
Citation(s):

Eckman MH et al. Cost-effectiveness of using pharmacogenetic information in
warfarin dosing for patients with nonvalvular atrial fibrillation. Ann
Intern Med 2009 Jan 20; 150:73. (Subscription may be required)

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