Novel Oral Anticoagulants for Venous Thromboembolism with Special Emphasis on Risk of Hemorrhagic Complications and Reversal Agents

Warfarin was the only oral anticoagulant available for the treatment of venous thromboembolism for about half a century until the recent approval of novel oral agents dabigatran, rivoraxaban and apixaban. This presents new classes of medications less cumbersome to use. They do not require frequent laboratory monitoring or have nurmerous drug interactions. On the other hand it also poses a challenge to the physicians deciding which agent to use in specific patient populations, how to predict the bleeding risk compared to warfarin and between the different novel agents and how to manage bleeding with relatively recent discovery of few potential antidotes. This review summarizes the major trials that led to the approval of these agents and their exclusion criteria helping physicians understand which patient types might not benefit from these agents. It provides clinical pearls invaluable in everyday practice such as transitioning between traditional and novel anticoagulants, dose adjustments for high risk populations, drug interactions and cost analysis. Futhermore, the review provides direct comparisons with warfarin and indirect comparisons among the novel agents in terms of efficacy and bleeding risk narrating the numbers of patients with intracranial, gastrointestinal and fatal hemorrhages in each of the major trials. We hope that this review will help the physicians inform their patients about the benefits and risks of these agents and enable them to make an informed selection of the most appropriate anticoagulant.