|Home | About | Journals | Submit | Contact Us | Français|
Warfarin is an oral anticoagulant that is widely prescribed to prevent thromboembolic events in persons at increased risk. The optimal dose is difficult to establish because it can vary 10-fold among individuals due to clinical and demographic factors. Testing for variants of the vitamin K epoxide reductase complex 1 (VKORC1) and cytochrome P450 2C9 (CYP2C9) genes has been proposed for use in guiding the initial dose of warfarin, thus achieving optimal dosing more quickly and with lower risk of bleeding.
Pharmacogenetic testing to guide warfarin dose selection for individuals at risk of a thromboembolic event with the goal of shortening the time required to achieve a stable, effective dose and minimizing the risk of adverse effects.
Analysis of multiple single nucleotide polymorphisms (SNPs) in VKORC1 and CYP2C9.
Over 31 million warfarin prescriptions were dispensed in 2004. Bleeding from warfarin use is a common adverse event and can cause substantial morbidity and mortality.
Systematic evidence reviews
Rapid ACCE review  from 2008 includes a discussion of ELSI issues and identifies knowledge gaps.
Recommendations by independent group*
Guidelines by professional group
2008 American College of Medical Genetics (ACMG) policy statement: "There is insufficient evidence, at
this time, to recommend for or against routine CYP2C9 and VKORC1 testing in warfarin-naive patients."
2008 American College of Chest Physicians guideline statement: "We suggest against pharmacogeneitc-based dosing until randomized data indicate that it is beneficial."
Some additional guidelines and recommendations can be found at Centers for Medicare & Medicaid Services Decision Memo for Pharmacogenomic Testing for Warfarin Response (CAG-00400N)(dated 8/3/2009):
* independent groups include the US Preventive Services Task Force (USPSTF) and Evaluation of Genomic Applications in Practice and Prevention (EGAPP) Working Group.
Test accuracy and reliability in identifying alleles at multiple SNPs (analytic sensitivity and specificity).
Clinical Validity:Test accuracy and reliability in predicting appropriate warfarin dose (predictive value).
Recent additions to the literature:
Last updated: April 12, 2010