Edoxaban: an Investigational Factor Xa Inhibitor

Atrial fibrillation (AF) is the most common cardiac arrhythmia, with an increased prevalence in older adults.1 The estimated lifetime risk of developing AF is one in four for both men and women older than 40 years of age.2 AF is also an independent risk factor for stroke. This increased risk for stroke is present in younger patients and increases significantly with advancing age.3 The primary modality for reducing the risk of stroke in patients with AF is chronic anticoagulation.4 Venous thromboembolism (VTE) is another serious condition in which an imbalance exists between clotting factors and endogenous anticoagulants, resulting in thrombosis. There are many risk factors for the development of VTE; blood clots can affect a wide variety of patients from ambulatory to institutional settings. Prevention and treatment options include both parenteral and oral medications.5 Over the past few years, a number of new oral anticoagulants have been approved for the treatment of patients with AF, VTE, or both. Prior to the approval of dabigatran, rivaroxaban, and apixaban, warfarin was the only oral anticoagulant available in the United States. In October 2010, dabigatran was approved by the Food and Drug Administration (FDA) and became the only oral direct thrombin inhibitor available for reducing the risk of stroke and systemic embolism in patients with nonvalvular AF; more recently, dabigatran was approved for the treatment of and reduction in the risk of recurrent VTE.6 In November 2011 and December 2012, the FDA approved rivaroxaban and apixaban, respectively. These oral factor Xa inhibitors are indicated for the prevention of stroke and systemic embolism associated with nonvalvular AF, for the prevention of VTE in patients following knee or hip replacement surgery, and for the treatment of VTE and the reduction in the risk of recurrent VTE.7,8 In January 2014, the Daiichi Sankyo Company submitted a new drug application (NDA) for another oral direct factor Xa inhibitor, edoxaban (Savaysa). Approval has been requested for the following indications: reduction in the risk of stroke and systemic embolic events in patients with nonvalvular AF; treatment of deep vein thrombosis (DVT) or pulmonary embolism (PE); and prevention of recurrent symptomatic VTE.9 Promising results from large clinical studies suggest that this new anticoagulant will likely be a competitor to the other oral treatment options mentioned above.9 Table 1 provides an overview of the oral anticoagulants. Table 1 Overview of Oral Anticoagulant Agents in the U.S. PHARMACOLOGY AND MECHANISM OF ACTION Edoxaban is a highly specific, direct inhibitor of factor Xa.10 Under normal circumstances, coagulation factors are successively activated along both intrinsic and extrinsic pathways that converge with the activation of factor Xa. Thrombin and fibrin are subsequently generated, leading to the production of a fibrin clot.11