Genotype-based dosing of oral anticoagulants requires additional evidence of protection against negative outcomes like severe bleeding to gain widespread acceptance over standard testing.
Does genotype-based dosing of 4-hydroxycoumarin anticoagulants improve anticoagulation outcomes compared to standard dosing?
Widespread clinical adoption of pharmacogenomic testing for warfarin dosing requires further evidence demonstrating improved clinical outcomes, such as reduced severe bleeding, across diverse populations.
Oral anticoagulants of the 4-hydroxycoumarin class, typified by warfarin, are used worldwide to treat thromboembolic disease. These drugs show the beneficial attributes of high efficacy and low cost, but patient management can be complicated by their narrow therapeutic index and wide inter-individual variability in dosing. Our understanding of the latter complication has improved significantly in recent years due to intense investigation of genetic factors influencing drug pharmacokinetics (CYP2C9) and pharmacodynamic response (VKORC1). In particular, the discovery of polymorphisms in the VKORC1 gene that strongly impact oral anticoagulant dose has heightened expectations that genetic testing for a relatively small cadre of warfarin-response genes might substantially enhance patient care in this area, especially during the initiation phase of therapy. However, enthusiasm for genotype-based dosing of oral anticoagulants must be balanced against the ready availability of both a simple phenotypic test (prothrombin time) and an antidote to over-anticoagulation (vitamin K). Wide-spread acceptance of genetically based tests for establishing therapy with warfarin and its congeners will likely require additional evidence that such an approach offers protection against a variety of negative anticoagulation outcomes, especially severe bleeding, as well as offering utility across many racial populations. This article will review recent events in these and other related areas.
Au et al. (Tue,) conducted a review in Thromboembolic disease. Genotype-based dosing of oral anticoagulants vs. Phenotypic testing (prothrombin time) was evaluated. Genotype-based dosing of oral anticoagulants requires additional evidence of protection against negative outcomes like severe bleeding to gain widespread acceptance over standard testing.
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