Thromboembolism involving the arterial or venous circu-lation or arising from the heart is a common cause of morbidity and mortality. Rapidly acting parenteral anticoagulants, such as heparin, are used for the prevention and initial treatment of thromboembolism and during revascularization procedures, 1 whereas the slower-acting vitamin K antagonists (VKAs) are used for long-term therapy. 2 The introduction of low-molecular-weight heparin (LMWH) and fondaparinux has simplified parenteral anticoagulant therapy, and these agents have replaced heparin for many indications. 3 Development of new oral anticoagulants to replace VKAs has been slower than that of parenteral agents. Ximelagatran, an oral thrombin inhibitor, was briefly licensed in Europe but was withdrawn in 2006 because of potential hepatic toxicity. 4 Although this set the field back for several years, the situation has changed with the recent introduction of dabigatran etexilate, a new oral thrombin inhibitor, and rivaroxaban, an oral factor Xa (fXa) inhibitor. 3 Licensed in Europe and Canada for prevention of venous thromboembolism (VTE) in patients undergoing hip or knee arthroplasty, dabigatran etexilate and rivaroxaban streamline out-of-hospital thromboprophylaxis because the drugs can be given once daily in fixed doses without coagulation monitoring. The greater unmet medical need, however, is to find a replacement for VKAs for long-term therapy, particularly stroke prevention in patients with atrial fibrillation (AF). The results of the Randomized Evaluation of Long-Term Anticoagulant Therapy (RE-LY) trial, which compared dabigatran etexilate with warfarin for stroke prevention in patients with AF, demonstrate that the new oral anticoagulants have the potential to be more effective and safer than VKAs. 5 If these results are replicated with other agents and in additional clinical settings, then oral thrombin and fXa inhibitors will soon replace VKAs.

This article (1) outlines the limitations of established parenteral and oral anticoagulants,(2) describes the potential advantages of the new agents,(3) briefly reviews the pharmacology and clinical trial results with new anticoagulants in advanced stages of development, and (4) provides perspective on the opportunities and challenges with the new parenteral and oral anticoagulants.