Systematic Evidence Reviews

An evidence-based review conducted in 2006 by the American College of Medical Genetics (Flockhart et al., 2008) found that CYP2C9 and VKORC1 testing to guide warfarin dosing had analytic and clinical validity. However, the review found that “no study has yet shown this intervention to be effective in reducing the incidence of high INR values, the time to stable INR, or the occurrence of serious bleeding events.” A recent systematic review by Kangelaris and colleagues also reported a lack of evidence of benefit (Kangelaris et al., 2009).

Regulatory Guidance

On January 22, 2010, the FDA modified the drug label for warfarin to include dose ranges based on pharmacogenomic information. This was an update to the 2007 label change that had added information about the association between CYP2C9 and VKORC1 variants and warfarin responsiveness. Both label changes inform the prescriber about the association between genotype and warfarin dosing requirements, but they do not require pharmacogenetic testing.

Guidelines by Professional Groups

The 2008 American College of Chest Physicians anticoagulation management guidelines state, “[W]e suggest against pharmacogenetic-based dosing until randomized data indicate that it is beneficial (Grade 2C)” (Ansell et al., 2008).

Recommendations by Payers

CMS recently issued a coverage decision for warfarin pharmacogenomic testing that specifies testing will be reimbursed only for patients initiating warfarin who are enrolled in a randomized controlled trial that measures major bleeding and thromboembolic events.


Analytic Validity

Testing for the two to three informative CYP2C9 SNPs and the single informative VKORC1 SNP is straightforward.

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