Warfarin Genotyping Reduces Hospitalization Rates: Results from the Medco-Mayo Warfarin Effectiveness Study (MM-WES)

Authors: Robert S. Epstein, MD, MS¹; Thomas P. Moyer, PhD²; Ronald E. Aubert, PhD¹; Dennis J. O’Kane, PhD²; Fang Xia, PhD¹; Robert R. Verbrugge, PhD¹; Brian F. Gage, MD, MS³; J. Russell Teagarden, DMH, RPh¹

Study in Brief:
- Warfarin, marketed under the brand names Coumadin^® and Jantoven^® and by generic drug manufacturers and distributors, is a commonly prescribed blood thinner that is exceptionally difficult to properly dose due to widely varying patient responses caused to a significant extent by genetic variations in the genes that determine the functional integrity of two important enzymes, CYP2DC and VKORC1.

- This comparative effectiveness study examined the impact incorporating genetic information into the management of warfarin treatment on hospitalization during the first six months of therapy, the period of time when most adverse events from warfarin occur.

- Hospitalization rates of 896 patients given a gene test for warfarin sensitivity when initiating drug therapy were compared to a control group of 2,688 patients who had begun warfarin treatment the prior year but had not received a genetic test.

- Study participants ranged in age from 40 to 75, were from 49 different states, and were covered by 29 different health plan sponsors managed by Medco and treated in a variety of medical practice settings.

- Results were evaluated in two ways: One included all hospitalizations from the time of the initial warfarin treatment even if genotyping had not yet occurred and was defined as the intention-to-treat (ITT) analysis; the other only included hospitalizations that occurred after genotyping and was called the per protocol (PP) analysis.

- The results showed that for the ITT analysis, patients who had been genotyped had a 31% lower rate of hospitalization for any cause and a 28% lower rate of hospitalization due to bleeding or blood clots than patients using the blood thinner who had not been given a genetic test.

- The difference was even more pronounced for the PP analysis, with genotyped patients having a 33% lower rate of hospitalization for any cause and a 44% lower rate than the control group for bleeding or thromboembolism.

¹Department of Medical and Analytical Affairs, Medco Health Solutions, Inc., Franklin Lakes, NJ
²Division of Clinical Biochemistry and Immunology, Mayo Clinic, Rochester, MN
³Department of Internal Medicine, Washington University, St. Louis, MO