From
U.S. News & World Report:
A DNA test could make prescribing the widely used anticoagulant
warfarin safer by predicting the lowest effective dose, a new study finds.
Because an effective dose of warfarin can vary as much as 10-fold from one person to the next, doctors start most people on a low dose and increase it until blood tests indicate the dose is correct. That process can take months.
For the study, which is published in the Feb. 19 issue of the New England Journal of Medicine, researchers collected demographic and genetic data on people at risk for stroke, heart disease and other problems related to blood clotting. The ideal doses of warfarin for these individuals had already been established by trial and error.
In addition, they looked at variants of two genes: CYP2C9, which affects how the liver activates and excretes warfarin, and VKORC1, which activates vitamin K, essential for blood clotting.
They used the data to create an algorithm that would predict the ideal dose of warfarin in a study of more than 4,000 people.
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.
"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.
Dr. Richard C. Becker, 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.