Investigational treatments of venous thromboembolism

Abstract

The antithrombotic management of venous thromboembolism (VTE) has gone through major developments. Indirect inhibitors such as low molecular weight heparin and the pentasaccharide fondaparinux represent improvements over traditional drugs such as unfractionated heparin for acute treatment of VTE with more targeted approaches, predictable pharmacokinetic profiles and lack of need for monitoring. Vitamin K antagonists, with inherent limitations of multiple food and drug interactions and frequent need for monitoring, remain the only oral anticoagulants approved for long-term secondary thromboprophylaxis in VTE with the removal of the oral direct thrombin inhibitor ximelagatran from the world market due to safety concerns. Newer anticoagulant drugs such as parenteral pentasaccharides (idraparinux and SSR-126517-E), oral direct thrombin inhibitors (dabigatran), oral direct Factor Xa inhibitors (rivaroxaban, apixaban, YM-150 and DU-176b) and tissue factor-Factor VIIa complex inhibitors (NAPc2) are tailor-made to target specific procoagulant complexes and have the potential to greatly expand our antithrombotic armamentarium for both acute and long-term treatment of VTE, especially as non-monitored parenteral and oral anticoagulants with a wide therapeutic window and a predictable anticoagulant response.