Embolism, Embolism and Thrombosis, Thromboembolism, Thrombosis, Vascular Diseases, Venous Thromboembolism, Warfarin
Conditions
Keywords
CYP2C9, VKORC1, polymorphism, warfarin, Coumadin
Brief summary
The purpose of this quasi-experiment study, which could also be classified as a prospective observational intervention study, is to assess the impact of cytochrome P450 2C9 (CYP 2C9) and vitamin K epoxide reductase complex, subunit 1 (VKORC1) testing within a primary patient care setting.
Detailed description
Anticoagulation therapy with warfarin is the most common mode of treatment and prophylaxis for venous and arterial thromboembolic conditions. Warfarin is metabolized in the liver by the cytochrome P450 system, the cytochrome P450 2C9 (CYP 2C9) isoenzyme specifically, and polymorphisms in the CYP 2C9 gene have been associated with changes in metabolic function of the translated isoenzyme . These polymorphisms result in reduced metabolism of warfarin as compared to subjects having the wild type gene, consequently leading to systemic accumulation of warfarin; it is theorized that this leads to higher risk of adverse events. Other allelic variations have also been linked to changes in vitamin K conservation through their effects on vitamin K epoxide reductase complex, subunit 1 (VKORC1) . The combined impact of CYP 2C9 and VKORC1 polymorphisms on warfarin's pharmacology have recently been reported. It is hypothesized that evaluation of genomic allelic type guided warfarin dosing will reduce thromboembolic and bleeding risks associated with warfarin therapy, and that adoption of a genetic testing strategy in a primary patient care setting would improve warfarin effectiveness and patient safety, and reduce costs to health care payers.
Interventions
OTHERCYP 2C9 and VKORC1 Testing for Warfarin
Test patients for their warfarin sensitivity and provide this information to their physician authorizing the test.
Sponsors
Mayo Clinic
Washington University School of Medicine
Medco Health Solutions, Inc.
Study design
Observational model
COHORT
Time perspective
PROSPECTIVE
Eligibility
Sex/Gender
ALL
Age
40 Years to 75 Years
Healthy volunteers
No
Inclusion criteria
* Female and male age range of 40-75 * Patients who are in the induction phase of warfarin * Patients receiving warfarin to prevent or treat thromboembolic conditions (e.g., post orthopedic surgery prophylaxis, deep venous thrombosis, atrial fibrillation, pulmonary embolism, heart failure) * Patient willing to provide informed consent prior to the specimen collection procedure * Patient whose physician is willing to order the genetic test
Exclusion criteria
* Age \< 40 or \> 75 * Previous use of warfarin within 180 days of initiating new warfarin therapy * Hospitalized for seven or more days before first claim for warfarin * Previous history of genetic testing for warfarin therapy * Known hypersensitivity to warfarin * Patient or physician refusal to participate in the study * Patients using warfarin residing in Olmsted County, MN
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| The primary objective of the study is to determine whether the addition of genotyping to usual care will reduce the hospitalization rates for hemorrhage or thromboembolism related to warfarin use during the first 6 months of treatment. | 6 months |
Secondary
| Measure | Time frame |
|---|---|
| The secondary objective is to determine physician and patient acceptance of the technology. | 6 months |
Countries
United States
Outcome results
None listed