Advances in Anticoagulants

Abstract

Utilizing the previously discussed in vitro and in vivo models for the evaluation of new anticoagulants resulted in recent advances in the development of novel oral anticoagulants (NOA). Major advances in the development of NOA progressed well, with the goal of developing safe and effective oral anticoagulants that do not require frequent monitoring or dose adjustment along with minimal food/drug interactions. Indirect inhibitors such as low-molecular-weight heparin (LMWH) and the pentasaccharide fondaparinux represent improvements over traditional drugs such as unfractionated heparin for acute treatment of venous thromboembolism (VTE) with more targeted anticoagulant approaches, predictable pharmacokinetic profiles, and lack of need for monitoring. Vitamin K antagonist, with its inherent limitations of multiple food and drug interactions and frequent need for monitoring, remains the only oral anticoagulant approved for long-term secondary thromboprophylaxis in VTE. The oral direct thrombin inhibitor ximelagatran was withdrawn from the world market due to safety concerns. Newer anticoagulant drugs such as injectables (fondaparinux, idraparinux), oral direct thrombin inhibitors (dabigatran), oral direct factor Xa inhibitors (rivaroxaban, apixaban, and others), and tissue factor/factor VIIa complex inhibitors are “tailor-made” to target specific procoagulant complexes and have the potential to greatly expand oral antithrombotic targets for both acute and long-term treatment of VTE, acute coronary syndromes, and prevention of stroke in atrial fibrillation patients.