For physicians administering warfarin (Coumadin, Bristol-Myers Squibb) treatment to patients in the outpatient setting, genotyping may help reduced hospitalizations that stem from bleeding or thromboembolism events, according to a study published June 22 in the Journal of the American College of Cardiology.
According to the authors, warfarin, used to prevent and treat thromboemboli, is started in almost two million patients in the U.S. per year, but is the second leading cause for emergency department visits and projects very high rates of mortality. Additionally, researchers say its difficult to reach a stable, effective dose.
Robert S. Epstein, MD, from Medco Health Solutions in Franklin Lakes, N.J., and colleagues conducted the MM-WES (Medco-Mayo Warfarin Effectiveness Study) trial to evaluate whether or not genotyping in patients who were on warfarin therapy was beneficial.
According to the authors, two genes—hepatic isoenzyme cytochrome (CYP2C9) and VKOR complex subunit 1 (VKORC1)—have previously been shown to predict individualized patient responses to warfarin dosage.
During the study, researchers evaluated hospitalization rates as a primary outcome in 896 patients undergoing warfarin genotyping compared to 2,688 patients in the historically matched control group over a six-month period.
Patients were drawn from member populations of prescription benefit plans and underwent free genotype testing with physician approval. Overall, the mean patient age was 65, and 61 percent were male.
Patient deoxyribonucleic acid for the two genes were collected, and results were delivered to physicians for interpretation. The Mayo Clinic then conducted genotype testing on the 896 patients.
For patients in the genotype cohort, 29.2 percent had normal warfarin sensitivity, 25.4 percent had lower-than-normal sensitivity, 12.2 percent had mild sensitivity, and 33.2 percent had moderate to very high sensitivity (suggesting a lower dose might be needed).
The researchers found that 58.6 percent of patients with less-than-normal, moderate, high or very high sensitivity could have received a potentially higher or lower dose than usual.
Additionally, results showed that patients in the genotyping arm had a 28 percent lower rate of all-cause hospitalizations compared to those in the control group.These intention-to-treat rates were 25.52 percent in the control group compared with 18.45 percent in the intervention group.
Intention-to-treat rates factored in adverse events that occurred in the control group if they occurred before the completion of genotyping.
The hospitalization rate for bleeding specific incidence was 27 percent lower in the intervention group compared to the control group, 6 percent versus 8.1 percent.
In a pre-protocol analysis, researchers found that there was a 33 percent lower risk of all-cause hospitalization and 43 percent lower risk for bleeding or thromboembolism hospitalizations compared to the control group.
“[W]e found significant reductions in adverse events for patients who were genotyped early in the course of warfarin treatment,” the authors wrote. “Our findings suggest that the addition of genotyping to usual care reduces the risk of hospitalization by approximately 30 percent among patients initiating warfarin.”
The authors concluded that the decline in hospitalizations related to warfarin usage could also offset some or all of the costs associated with warfarin genotyping. “Although an economic analysis is outside the scope of this report, our data should help to determine the net financial cost of paying for genotype testing as a component of warfarin therapy,” the authors concluded.
In an accompanying editorial, Geoffrey S. Ginsburg, MD, PhD, and Deepak Voora, MD, from Duke University in Durham, N.C., wrote “Beyond the research agenda for pharmacogenetics, there are policy issues that need to be concurrently addressed for the path to adoption to be a clear one.”
Ginsburg and Voora said that health systems should be looking to implement pharmocogentic-based testing into practice but should understand that physician education, the reimbursement of testing and the infrastructure to perform this genetic testing is important and is required.
“Until we lay the groundwork for developing the appropriate evidentiary path for pharmacogenetic testing, personalized medicine will remain an often-cited goal that remains on the research horizon without any tangible benefits for patients,”