A simple genetic test that helps physicians determine for each patient the safest and most effective dose of an anticoagulant significantly reduces the number of hospitalizations during the critical start-up phase when dosing is typically adjusted by trial and error, according to research presented at the American College of Cardiology's 59th annual scientific session.

The Medco-Mayo Warfarin Effectiveness Study (MM-WES) found that hospital admissions for any cause could be cut by nearly one-third, as could hospitalizations for either excess bleeding or unwanted blood clotting simply by testing for variations in two genes that strongly influence a patient's sensitivity to the blood thinner warfarin.

"Genetic testing is a tool clinicians can use to more accurately predict the best warfarin dose early on," said Robert S. Epstein, M.D., chief medical officer and president of the Medco Research Institute in Franklin Lakes, N.J. "Patients may get to a stable dose more quickly and, therefore, have a lower risk of negative outcomes."

Warfarin sensitivity varies widely, however, and it can take weeks or even months of repeated blood tests and dose adjustments to determine the right dose for each patient. During that time, patients are at high risk for either thromboembolism from too little warfarin, or dangerous bleeding from too much warfarin. The MM-WES study is the first national, prospective, comparative effectiveness study to evaluate the role of genetic testing in assisting physicians to gauge the best warfarin dose and monitoring intensity during the early dose-adjustment phase of treatment.

For the study, researchers recruited 896 patients who were beginning warfarin therapy. All study participants were members of a prescription benefits plan managed by Medco Health Solutions. They came from 49 of 50 states and a variety of practice settings.

Shortly after starting warfarin therapy, patients gave a blood sample or a cheek swab, which was analyzed at the Mayo Clinic in Rochester, M.N. For each patient, the ordering physician received a report on the genetic expression of two genes, CYP2C9 and VKORC1, as well as clinical information on how to interpret the findings. For example, a patient might be classified as having a high sensitivity to warfarin based on genotype. In this case, the physician would be advised to reduce the warfarin dose and monitor blood tests more frequently. If a patient were found to have a low sensitivity to warfarin, the report would recommend an increase in warfarin dose. Each physician was free to decide how to respond to the report and what action to take.

The researchers found that, during the first six months of warfarin therapy, patients who had genetic testing were 31 percent less likely to be hospitalized for any cause, when compared to an historical control group that did not undergo genetic testing. Patients in the gene-testing group were also 29 percent less likely to be hospitalized for bleeding or thromboembolism. The study's findings were even stronger when the analysis included only hospitalizations that occurred after genotyping. In this per-protocol analysis, patients who underwent genetic testing had a 33 percent lower risk of all-cause hospitalization and a 43 percent lower risk of hospitalization for bleeding or thromboembolism.

The cost of genetic testing - approximately $250 to $400, depending on the laboratory - is justified by the savings, according to Epstein. "If we reduce just two hospitalizations per 100 patients tested, that more than compensates for the cost of genotyping," he said.

Medco provided funding for genotyping and data collection. Researchers from the Mayo Clinic and Washington University donated their time.