Researchers seek to determine ideal individual dosages of warfarin through genetics

Researchers at Newcastle and Liverpool universities in England plan to test whether or not genetics could impact personalized medicine by optimizing each patient’s dose of warfarin, a common blood-thinning drug.

Scientists have reported that two genes, CYP2C9 and VKORC1, which vary slightly among different individuals, can influence warfarin’s effectiveness. Now investigators want to determine whether information about these genes could improve decisions on the amount of warfarin given to a patient at the start of treatment.

“The way different patients respond to warfarin is notoriously unpredictable, particularly at the very start of treatment,” Farhad Kamali, PhD, a professor at Newcastle University and leader of the trial alongside colleague and fellow professor Ann Daly, said in a press release. “Now we know that certain genes can affect the way individual patients respond to warfarin [and] we can use this information to personalize therapy. This clinical trial will be able to demonstrate whether the gene-guided dosing can optimize the safety of anticoagulation therapy.”

Using information from thousands of patients, an international team of researchers — including those at Liverpool and Newcastle universities in England — have developed a mathematical formula using patient’s genetic information that could help doctors better determine optimal warfarin doses.

The results of the analysis are published in the Feb. 19 issue of The New England Journal of Medicine.

The scientists calculated warfarin dosages in three ways: using the standard clinical information; including additional information about individual patient variation in CYP2C9 and VKORC1; and using a fixed dose per day. They then checked how closely their computational predictions matched the actual, clinically derived, stable warfarin dosage for each patient, according to the press release.

The results revealed that when researchers included the patient’s genetic information in their assessments, the predictions of ideal dosages were more accurate, especially for patients at the low or high ends of the dosing range. Nearly half of the patients who take warfarin are at the extremes of the range, Kamali said in the press release, and these patients are typically at the greatest risk for excessive bleeding or clotting.

By quickly optimizing dosages for these patients, doctors could minimize dangerous complications and improve the effectiveness and safety of warfarin treatment, he said in the press release.

Reference:
Kamali F, Daly A. Estimation of the warfarin dose with clinical and pharmacogenetic data. New Eng J Med. 360;8:753-764.