Genetics May Help Fine-Tune Warfarin Dosage

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The researchers found that the algorithm predicted the ideal dose of warfarin better than other approaches.

Specifically, the algorithm's predictions were, on average, within about 8.5 milligrams of a person's ideal weekly dose. Demographic and clinical data alone predicted doses of about 10 milligrams off the ideal weekly dose, and a method that used a fixed daily dose, or about 35 milligrams a week, was off by an average of 13 milligrams, the researchers found.

"Warfarin has a very narrow therapeutic range," said co-author Teri Klein, a senior research scientist in genetics at Stanford. "Overdosing and underdosing of warfarin results in patients either being at much greater risk for excessive bleeding [overdosing] or clotting [underdosing]," she said.

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"We found, based on this population, that 46 percent of the population would benefit by including their genotypes for these two genes," Klein said. "By including the genotypes along with clinical and demographic information, initial dosing is much closer to the ideal dose, thus limiting potential adverse events."

Altman said a trial now is needed to see if people who are prescribed warfarin based on genetic testing actually do better than those whose dosage is not determined with the aid of genetics.

"More broadly," he said, the study's finding "tells us that the day when we routinely use genetic information to personalize the use of drugs is coming and may be almost here for warfarin."

Dr. Richard C. Becker, a professor of medicine in the divisions of cardiology and hematology at Duke University School of Medicine, said that the researchers appear to be on the right track but that more testing is needed before the approach becomes standard practice.

"The safe and effective use of medications based on patient-specific needs is an achievable goal in the early 21st century," Becker said. "Genetic testing added substantially to traditionally employed daily dose prediction methods, particularly among patients with low dose requirements."

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