Genetic Warfarin Dosing: Tables Versus Algorithms
What is the most accurate way to predict warfarin dosing?
This was a retrospective cohort study of 1,378 patients with stable therapeutic warfarin dosing and complete genetic and clinical data. Five dose prediction methods were compared: two methods using only clinical information (empiric 5 mg/day dosing and a formal clinical algorithm), two genetic tables (the new warfarin label table and a table based on mean dose stratified by genotype), and one formal pharmacogenetic algorithm, using both clinical and genetic information. For each method, the proportion of patients whose predicted doses were within 20% of their actual therapeutic doses was determined.
Warfarin dose prediction was significantly more accurate (all p < 0.001) with the pharmacogenetic algorithm (52%) than with all other methods: empiric dosing (37%; odds ratio [OR], 2.2), clinical algorithm (39%; OR, 2.2),warfarin label (43%; OR, 1.8), and genotype mean dose table (44%; OR, 1.9).
Although genetic tables predicted warfarin dose better than empiric dosing, formal pharmacogenetic algorithms were the most accurate.
Anticoagulation with warfarin can be challenging as genetic and non-genetic factors can affect dose response. Bleeding or thrombosis may occur if the narrow therapeutic international normalized ratio range is not achieved. Some studies have indicated that testing for genetic variants affecting warfarin activity may lead to more accurate dose prediction with reduced rates of hospitalization. The current study indicates that a formal pharmacogenetic algorithm (available online) is superior to the genetic tables provided in the warfarin label. However, even with this testing, 48% of patients were not dosed accurately. Until warfarin is replaced by more predictable oral anticoagulant agents, these algorithms might be considered for use in patients treated with warfarin.
Keywords: Thrombosis, Warfarin, Genotype, Pharmacogenetics
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