Oral Direct Factor Xa Inhibitors

Abstract

Vitamin K antagonists, such as warfarin, have been the mainstay of oral anticoagulation for many decades. Although effective, warfarin has numerous limitations, including a variable dose requirement from patient to patient because of differences in dietary vitamin K intake, common genetic polymorphisms, and multiple drug interactions that affect its pharmacodynamics and metabolism. Consequently, warfarin requires frequent monitoring to ensure that a therapeutic anticoagulant effect has been achieved because excessive anticoagulation can lead to bleeding, and because insufficient anticoagulation can result in thrombosis. Such monitoring is burdensome for patients and physicians and is costly for the health care system. These limitations have prompted the development of new oral anticoagulants that target either factor Xa or thrombin. Although the path to the development of these drugs has been long, the new drugs are at least as effective and safe as warfarin, but they streamline clinical care because they can be administered in fixed doses without routine coagulation monitoring. This article focuses on rivaroxaban, apixaban, and edoxaban, the oral factor Xa inhibitors in the most advanced stages of development. After 20 years of discovery research, these agents are already licensed for several indications. Thus, the long path to finding replacements for warfarin has finally reached fruition. Therefore, development of the oral factor Xa inhibitors represents a translational science success story.

Evolving Treatments for Arterial and Venous Thrombosis

“…2,3 Ximelagatran, a reversible inhibitor of thrombin, was the first direct oral anticoagulant (DOAC) licensed for clinical use. 4,5 Although withdrawn which inhibit factor Xa.…”

Dynamics of Thrombin Generation and Flux from Clots during Whole Human Blood Flow over Collagen/Tissue Factor Surfaces

“…Direct thrombin or Factor Xa (FXa) inhibitors are orally available and clinically approved and do not requiring frequent coagulation monitoring in patients (35). The reduction of thrombotic risk, although still allowing for sufficient hemostasis to prevent undesired bleeding, is central to therapeutic potency and dosing.…”

Comparisons between Novel Oral Anticoagulants and Vitamin K Antagonists in Patients with CKD

“…Thrombin and factor Xa are targeted by the NOACs for anticoagulant therapy given their roles in clot formation. 7,8 Advantages of the NOACs include their rapid onset of action, shorter half-lives, lack of requirement for regular laboratory monitoring, and absence of food interactions compared with VKAs.…”