Novel oral anticoagulants

Abstract

Warfarin has a proven record as an oral anticoagulant; almost every study, however, has found that it is not prescribed for 40-60% of patients who are eligible and should receive it, and of those who do receive it, serum warfarin levels only achieved a time in therapeutic range (TTR) equal to INR 2-3 about 55-60% of the time (online video available at: http://education.amjmed.com/video.php?event_id=445&stage_id=5&vcs=1). This means that only about 1 in 4 patients are adequately anticoagulated with warfarin, and thus there is a large unmet need for achieving better anticoagulation in these patients. Although physicians have sometimes tried to use antiplatelet therapy (aspirin, plus or minus clopidogrel) for anticoagulation, this may result in as much as a doubling of the risk of thromboembolic events. Recently 2 new classes of oral anticoagulant agents have appeared: direct thrombin inhibitors (DTIs) and factor Xa inhibitors. This review sequentially examines the recent clinical trial evidence for the 3 approved NOACs in the 2 classes, highlighting that all 3 share a class effect of being noninferior to warfarin for reducing risk of stroke and systemic embolization and reducing risk of bleeding, with a relative risk of mortality consistently reduced by 10% per year. In addition, all of the NOACs have a significantly lower risk of intracranial/intracerebral bleeding than warfarin, an important clinical consideration, since that is the most feared bleeding risk and may be sufficient reason to consider switching patients from warfarin to a NOAC, even if they seem to be doing well on warfarin. Finally in addition to reviewing the overall benefits of these NOACs over traditional therapy, the clinical application differences between the classes and between the agents are reviewed.