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CLINICAL RESEARCH: CLINICAL TRIAL

Warfarin Genotyping Reduces Hospitalization Rates

Results From the MM-WES (Medco-Mayo Warfarin Effectiveness Study)

Robert S. Epstein, MD, MS^_*,_*, Thomas P. Moyer, PhD, Ronald E. Aubert, PhD^_*, Dennis J. O'Kane, PhD, Fang Xia, PhD^_*, Robert R. Verbrugge, PhD^_*, Brian F. Gage, MD, MS and J. Russell Teagarden, DMH, RPh^_*

^_* Department of Medical and Analytical Affairs, Medco Health Solutions, Inc., Franklin Lakes, New Jersey
Department of Laboratory Medicine and Pathology, Mayo Clinic, Rochester, Minnesota
Department of Internal Medicine, Washington University, St. Louis, Missouri

Manuscript received February 15, 2010; revised manuscript received March 9, 2010, accepted March 11, 2010.

^_* Reprint requests and correspondence: Dr. Robert S. Epstein, Department of Medical and Analytical Affairs, Medco Health Solutions, Inc., 100 Parsons Pond Drive, Franklin Lakes, New Jersey 07417 (Email: Robert_Epstein{at}medco.com).

Objectives: This study was designed to determine whether genotype testing for patients initiating warfarin treatment will reduce the incidence of hospitalizations, including those due to bleeding or thromboembolism.

Background: Genotypic variations in CYP2C9 and VKORC1 have been shown to predict warfarin dosing, but no large-scale studies have prospectively evaluated the clinical effectiveness of genotyping in naturalistic settings across the U.S.

Methods: This national, prospective, comparative effectiveness study compared the 6-month incidence of hospitalization in patients receiving warfarin genotyping (n = 896) versus a matched historical control group (n = 2,688). To evaluate for temporal changes in the outcomes of warfarin treatment, a secondary analysis compared outcomes for 2 external control groups drawn from the same 2 time periods.

Results: Compared with the historical control group, the genotyped cohort had 31% fewer hospitalizations overall (adjusted hazard ratio [HR]: 0.69, 95% confidence interval [CI]: 0.58 to 0.82, p < 0.001) and 28% fewer hospitalizations for bleeding or thromboembolism (HR: 0.72, 95% CI: 0.53 to 0.97, p = 0.029) during the 6-month follow-up period. Findings from a per-protocol analysis were even stronger: 33% lower risk of all-cause hospitalization (HR: 0.67, 95% CI: 0.55 to 0.81, p < 0.001) and 43% lower risk of hospitalization for bleeding or thromboembolism (HR: 0.57, 95% CI: 0.39 to 0.83, p = 0.003) in patients who were genotyped. During the same period, there was no difference in outcomes between the 2 external control groups.

Conclusions: Warfarin genotyping reduced the risk of hospitalization in outpatients initiating warfarin. (The Clinical and Economic Impact of Pharmacogenomic Testing of Warfarin Therapy in Typical Community Practice Settings [MHSMayoWarf1]; NCT00830570)

Key Words: warfarin • genotyping • pharmacogenomics • comparative effectiveness

Abbreviations and Acronyms   CI = confidence interval   HR = hazard ratio   INR = international normalized ratio   PP = per-protocol

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