Traditional anticoagulants, such as warfarin and enoxaparin, have several limitations, including parenteral administration, need for laboratory monitoring, and ongoing dose adjustment, which may limit optimal patient care. Newer oral anticoagulants, such as direct thrombin inhibitors (e.g., dabigatran etexilate) and direct factor Xa inhibitors (e.g., rivaroxaban, apixaban, and edoxaban), have been developed to overcome these drawbacks, and thereby improve patient care. Several of these agents have been approved for use in the prevention and treatment of venous and/or systemic thromboembolism. The objective of this paper is to provide an overview of the available clinical trial data for these new oral anticoagulants in the prevention and treatment of venous thromboembolism and a practical update for clinicians. 1. Introduction Venous thromboembolism (VTE) comprises deep vein thrombosis (DVT) and pulmonary embolism (PE). Although the exact incidence of VTE is not known, it is estimated to affect 900,000 patients each year in the United States [1]. Approximately one-third of these cases are fatal pulmonary emboli, and the remaining two-thirds are nonfatal episodes of symptomatic DVT or PE [1]. VTE is the second most common cause of extended hospital stay and the third most common cause of in-hospital mortality [2]. Because it causes considerable morbidity and mortality, VTE places a substantial burden on healthcare resources [3, 4]. Without thromboprophylaxis, the incidence of hospital-acquired DVT based on objective diagnostic screening is 10–40% among medical or general surgical patients and 40–60% among patients who have undergone major orthopedic surgery such as total knee replacement (TKR), total hip replacement (THR), and hip fracture surgery [5]. Patients with cancer are at a greater risk of new or recurrent VTE than patients without cancer. VTE risk is 3- to 5-fold higher in cancer patients who are undergoing surgery and 6.5-fold higher in cancer patients receiving chemotherapy than in patients who do not have cancer [6, 7]. The efficacy of traditional anticoagulants in preventing VTE in patients undergoing major orthopedic surgery and in hospitalized acutely ill medical patients is well established [5, 8–11]. However, these agents have several limitations that may limit optimal patient care, such as their parenteral administration, need for laboratory monitoring, and ongoing dose adjustment (Table 1) [12–16]. Newer oral anticoagulants, such as direct thrombin inhibitors (e.g., dabigatran etexilate) and direct factor Xa inhibitors (e.g.,
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