Oral direct factor Xa inhibitors, with special emphasis on rivaroxaban

Rivaroxaban is a small-molecule, direct factor Xa inhibitor that is under investigation for the prevention and treatment of venous and arterial thrombosis. To date, oral anticoagulants have been limited largely to vitamin K antagonists. Despite their remarkable benefits, vitamin K antagonists are limited by their narrow therapeutic window, the existence of multiple food and drug interactions, and the need for frequent monitoring and dose-adjustment. Rivaroxaban represents a potentially attractive alternative to warfarin, as it could enable simplified once-daily dosing, requires no therapeutic monitoring, and has a lower potential for drug interactions. At present, the safety and efficacy of rivaroxaban for the prophylaxis and treatment of venous thromboembolism has been evaluated in phase-II and phase-III trials involving over 24,000 patients. Rivaroxaban is also being evaluated for the treatment of pulmonary embolism, secondary prevention after acute coronary syndromes, and the prevention of stroke and non-central nervous system embolism in patients with non-valvular atrial fibrillation. The need for new oral anticoagulants, the development and pharmacology of rivaroxaban, results of completed studies of rivaroxaban, and details of ongoing phase-II and phase-III trials with rivaroxaban are the subjects of this chapter.