Warfarin-related genotyping is unlikely to be cost-effective for typical patients with non-valvular atrial fibrillation, but may be cost-effective in patients at high risk for hemorrhage who are starting warfarin therapy, according to a study in the Jan. 20 issue of the Annals of Internal Medicine.
Mark Eckman, MD, professor of medicine at the University of Cincinnati and lead investigator of the study, said that the FDA changed the labeling for warfarin in 2007, suggesting that clinicians consider genetic testing before initiating therapy.
“There are certain genes that are known to contribute to an increased sensitivity to warfarin," he said. “The idea behind genetic testing—also known as pharmacogenetic-guided dosing— is to help guide the initial, and possibly lower, dose of warfarin for patients found to possess certain variants of the genes cytochrome P450 CYP2C9 and vitamin K epoxide reductase, or VKORC1. The hope is that more accurate dosing will translate into decreased major bleeds during the initiation phase of warfarin dosing, which is the first month or so.”
The researchers said that they looked at whether the benefit of testing is worth the costs associated with it.
Researchers performed an analysis combining the results of the only three clinical studies published to date to determine the degree to which pharmacogenetic-guided dosing decreases the risk of major bleeds when compared with standard induction of treatment with warfarin. The team constructed a model to estimate the cost-effectiveness of a genotype-guided dosing strategy.
While they found that genotype-guided dosing resulted in better outcomes, it was at a relatively high cost—more than $170,000 per quality-adjusted life year gained.
In other analyses that took into consideration the limitations of the studies, researchers found that there is only a 10 percent chance that genotype-guided dosing is likely to be cost-effective. The researchers also looked at the impact of other variables on the cost-effectiveness of genotype-guided dosing.
Eckman said that results show that genotype-guided dosing might be worth the costs if it:
- Is used for patients at high risk for hemorrhage;
- Prevents more than 32 percent of major bleeding events;
- Is available within 24 hours; and
- Costs less than $200.
"This could be accomplished if testing were done in-house, at lower cost and without delays," he said, noting that currently in most cases these tests need to be sent to outside laboratories which can lead to delays in starting treatment and increased cost. "Furthermore, future studies, such as the recently funded National Institutes of Health COAG trial, need to examine the impact of pharmacogenetic-guided dosing on bleeding risk and monitor outcomes long enough to determine the true duration of benefit."
Eckman also suggested that rather than excluding patients at higher risk for bleeding, studies should offer enrollment if it has already been determined that these patients require warfarin.
"Personalized, predictive medicine offers great promise, but we need to carefully examine the benefits and understand the cost-effectiveness of such strategies before we spend a lot of money on very expensive tests,” Eckman concluded.
The National Institute of Diabetes and Digestive and Kidney Diseases; National Heart, Lung, and Blood Institute; Foundation for Informed Medical Decision Making; National Institutes of Neurological Disorders and Stroke; Deane Institute for Integrative Study of Atrial Fibrillation and Stroke; and American Heart Association (AHA) funded the study.