NEW YORK (Reuters Health) – Warfarin dosing based on genotype-stratified tables is more accurate than empiric dosing, but not as good as estimates derived from formal pharmacogenetic algorithms, investigators report in the Journal of the American College of Cardiology for February 1.

Dr. Stephen E. Kimmel, at the University of Pennsylvania School of Medicine, Philadelphia, and colleagues note that, recently, warfarin dose prediction has focused on the use of pharmacogenetic algorithms based on complex regression equations. To simplify this approach, last year the US Food and Drug Administration added a table of estimated warfarin dose, stratified by genotype, to the warfarin label.

To compare the accuracy of genetic tables with pharmacogenetic algorithms, the team conducted a retrospective cohort study of 1,378 patients taking warfarin. All had achieved a stable therapeutic dose of warfarin that produced therapeutic international normalized ratio (INR) values on 2 or 3 consecutive visits.

“Five dose prediction methods were compared,” the authors explain: empiric 5 mg/day dosing, a formal clinical algorithm, the new warfarin label table, a table based on mean dose stratified by genotype, and a formal pharmacogenetic algorithm using both clinical and genetic information.

The proportion of patients whose predicted doses were within 20% of their actual therapeutic doses with the five methods were 37% with empiric dosing, 39% for the clinical algorithm, 43% using the warfarin label table, 44% based on the genotype mean dose table, and 52% with the pharmacogenetic algorithm.

The latter was significantly more accurate than all the other methods at a p value of <0.001.

“As a result, it seems advisable for clinicians to use a formal pharmacogenetic algorithm instead of a genetic dosing table when feasible,” Dr. Kimmel and colleagues advise.

They add, “Should dosing algorithms prove effective at improving clinical outcomes in ongoing randomized trials, methods to improve access to these algorithms could include publication in the warfarin label, web-based access, and incorporation into handheld devices.”

Reference:
Genetic Warfarin Dosing: Tables Versus Algorithms
J Am Coll Cardiol 2011; 57:612–61.8