Findings from a recent study suggests that clinical and genetic factors affecting warfarin dose requirements differ by race. The study is published in the journal Blood.
A team of researchers from the University of Alabama at Birmingham have proposed race-specific equations to guide clinicians better calculate warfarin dosage. Factors such as height, weight, and genes that help break down warfarin and activate clotting (CYP2C9 and VKORC1) are thought to affect dose requirements.
The EU-PACT trial in 2013 concluded that genotype-guided dosing improved anticoagulation control. However, the COAG (Clarification of Optimal Anticoagulation through genetics) trial concluded that a similar genotype-guided strategy did not seem to make a difference among the evaluated patients. The COAG trial did enroll more African American than the EU-PACT (27% vs. 0.9% of population); the African Americans were found to fare worse after following genotype-guided therapy. The contrast in both studies’ results may be due to differences in racial diversity among the subjects, reported Nita Limdi, PhD, PharmD, MSPH.
In this study, Dr. Limdi and colleagues examined 1,357 patients treated with warfarin by calculating and comparing their recommended dose according to both race-adjusted and race-specific dosing models. They observed that genetic factors attributed to the dose variability among European Americans whereas clinical factors accounted for a larger variability in African Americans. Specifically, European Americans with a CYP2C9*2 variant required less of the drug based on race-specific dosing models, but African Americans did not. Patients who carried VKORC1 required less of the drug in general, but a greater proportional dose reduction was seen in European Americans.
Researchers recommend the use of race-specific equations rather than race-adjusted equations when calculating warfarin dosing due to genetic and clinical influence.
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