Current challenges in personalizing warfarin therapy

In an exciting era where novel oral anticoagulants, such as the factor Xa and direct thrombin inhibitors, are beginning to emerge as therapeutic options, the vitamin K antagonists (VKAs) such as warfarin, which have been in clinical use for over half a century, will remain an important part of the therapeutic landscape for the foreseeable future. The optimal effectiveness and safety of the VKAs is limited by significant inter- and intra- patient variability in dose response. As such, routine laboratory monitoring with subsequent dose adjustment to achieve and maintain an international normalized ratio (INR) that falls within a narrow therapeutic range is necessary; even with frequent INR monitoring, time in therapeutic range of VKAs is generally <60% in usual care settings. Yet, personalized approaches to warfarin therapy, such as the routine incorporation of pharmacogenetic data into dose selection and adjustment, the selective use of prescribed doses of vitamin K for those patients with unstable INRs, and integration of patient self-testing /self-management, has the potential to improve the safety, efficacy and ease of use of warfarin. To date, no randomized trials have proven the benefits of routine pharmacogenetic testing for warfarin initiation; however, pivotal trials are ongoing. Through further investigative work, allowing these personalized strategies to realize their full potential, warfarin may remain a preferred therapeutic oral anticoagulant for years to come.