Genetic Testing Doesn’t Improve Warfarin Dosing
Although warfarin is an effective therapy, determining the best dose for each patient can be tricky. Too much can cause excess bleeding; too little can lead to dangerous blood clots. Doctors often initially prescribe a standard dose based on clinical measures such as age, body size, smoking status, and use of certain medications. They then closely monitor the drug’s activity through blood tests and adjust the dose as needed.
Two genes are known to influence warfarin's effectiveness. One, called CYP2C9, deactivates warfarin. The other, VKORC1, activates vitamin K, which is essential for blood clotting. Variations in these genes may affect how a person responds to warfarin. Thus, dosing formulas have been developed to incorporate a person’s genetic profile, along with their clinical characteristics, to better predict the warfarin dose that person may need. This approach is known as pharmacogenetics.
To examine the success of using genetics in warfarin dosing, a team of researchers conducted a large clinical trial. More than 1,000 people, 46-70 years old, 51% male, 27% African-American, were randomly assigned to receive warfarin doses for the first 5 days of therapy based on their clinical and genetic characteristics or on their clinical characteristics alone.
Participants were followed for 23 additional days, during which time their drug doses were adjusted based on standard protocols. Both the participants and the treating physicians were blinded to the strategy and the dose of warfarin. The study was supported in part by NIH’s National Heart, Lung, and Blood Institute (NHLBI). Results appeared online on November 19, 2013, in the New England Journal of Medicine.
The investigators found that blood thinning was within a desired range 45% of the time in both groups during the 28-day monitoring period, based on standardized blood clotting tests. Adding genetic information to the dosing formula did not improve blood clotting control.
African-American participants whose dosing was based on the pharmacogenetic formula spent only 35% of time in the ideal range, compared to 44% of the time for those whose dosing was based on the clinical formula. Overall, there were no differences in adverse events, such as major bleeding, between the dosing groups.
“These findings highlight the importance of developing and evaluating pharmacogenetic testing in patients from diverse racial and ethnic backgrounds,” says NHLBI Director Dr. Gary H. Gibbons. “The use of genetic data holds great promise for predicting disease risk or determining optimal therapies, but it must be put to the test through clinical trials like this one to determine how to best use that information.”
- Personalized Medicine: Matching Treatments to Your Genes:
- Genetic Tests Help Optimize Doses of Blood-Thinning Drug:
- Frequently Asked Questions about Pharmacogenomics:
- Clarification of Optimal Anticoagulation Through Genetics (COAG) Research Study Site:
Funding: NIH’s National Heart, Lung, and Blood Institute (NHLBI).