New oral anticoagulants in development: potential for improved safety profiles

Venous thromboembolism is the most frequent preventable cause of death in hospitalized patients. Currently available anticoagulants have limitations that restrict their widespread use, particularly in long-term indications. Vitamin K antagonists require frequent monitoring and dose adjustment, and have a narrow therapeutic window with the risk of bleeding. The low-molecular-weight heparins have more predictable pharmacokinetics and pharmacodynamics, and coagulation monitoring is not required. However, their subcutaneous administration limits their suitability for long-term use. Consequently, many patients fail to receive effective preventive therapy. Rivaroxaban, apixaban, and dabigatran are new anticoagulants in late-stage clinical development that inhibit a single, specific coagulation factor, unlike the Vitamin K antagonists and low-molecular-weight heparins. Studies suggest that they provide effective, predictable anticoagulation with a low bleeding risk and will potentially offer an improved clinical profile and wider safety margin compared with currently available therapies.