Genetics Should Decide Warfarin Dose, Study Reiterates

March 20 (HealthDay News) -- Researchers have confirmed previously reported genetic factors that may help doctors more accurately prescribe the proper dosage of the blood thinner warfarin to people at high risk of cardiovascular problems.

According to U.S. Food and Drug Administration estimates, about 2 million Americans use the anticoagulant medication to prevent blood clots and reduce the likelihood of a stroke, pulmonary embolism or heart attack.

Though the drug can be very effective, the optimal therapeutic dosage varies as much as 20-fold among individuals, with too high a dose risking severe bleeding and too small a dose failing to protect against the original cardiovascular worry. Trial and error followed by frequent monitoring of blood levels have been the common method of determining the proper dose for a given person.

Researchers from Sweden and the United Kingdom, studying the genetic makeup of more than 1,000 warfarin users, reported finding three genes -- VKORC1, CYP2C9 and CYP4F2 -- with common variants that explain more than 40 percent of the variability in optimal dosing levels. VKORC1, which affects the liver's ability to use and excrete warfarin, and CYP2C9, which helps with the essential blot-clotting vitamin K, were found to be responsible for the vast majority of the variability, according to the study. The findings were to be published March 20 in PLoS Genetics.

The finding appears to support a study in the Feb. 19 issue of the  New England Journal of Medicine. In that report, American researchers collected data -- including the VKORC1 and CYP2C9 variants -- from more than 4,000 people taking warfarin and created an algorithm that had a high rate of success predicting the ideal dose of the drug.


SOURCES: PLoS Genetics, news release, March 19, 2009; New England Journal of Medicine, Feb. 19, 2009

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