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• Vol.51 No.11
• CLINICA NEUROL, 51: 1007−1010, 2011
• Vol.51 No.11 contents

Symposium 16

Current status and future of anti-Xa inhibitors

Takehiko Nagao, M.D.

Department of Neurology, Tokyo Women's Medical University

Anticoagulant therapy, known as warfarin, has been underused despite its marked benefit from embolic prevention. The intricate maintenance has made physicians constrained the use of warfarin for the many decades. Facing the 21^st century, several new anticoagulants which inhibit single coagulant factor, such as activated factor X (Xa) or activated factor II (thrombin), has been developed. We now have selective thrombin inhibitor, dabigatran, already rolled out in clinical practice around the world. Among these drugs, four new Xa inhibitors are in final developing stage. This article reviewed the current status of new Xa inhibitors. Rivaroxaban leads the other Xa inhibitors in distribution. The phase III clinical study called ROCKET AF study had been completed and recently published. Statistical non-inferiority was clearly established compared to regular warfarin therapy. The Japanese rolled J-ROCKET AF study with 1,000 patients and the usage of reduced dose of rivaroxaban has made a similar outcome and safety end points compared to the initial ROCKET AF study. ARISTOTLE study, a phase III clinical study of apixaban has also been finished this year and will be presented soon. A phase III study of using edoxaban, a Japanese manufactured Xa inhibitor, named ENGAGE AF-TIMI 48 will be completed by next year. Darexaban, another Japan-made Xa inhibitor is in its preparation of phase III trial following favorable results of its late phase II study (OPAL-2). Having every trial with its favorable outcome, multiple alternatives of Xa inhibitors will be out in practice in no distant future. In addition, we must be aware to have a deliberate evaluation for each result, even pharmacological profiles of each Xa inhibitors with a 12 hour half-life period shows similarity, the difference in twice-daily dosing with once a day, or the difference in severity of patients' atrial fibrillation risk factor each trial contains might affect the results of phase III trials.
Full Text of this Article in Japanese PDF (226K)

(CLINICA NEUROL, 51: 1007−1010, 2011)
key words: anticoagulant therapy, anti-Xa inhibitor, warfarin, atrial fibrillation, stroke

(Received: 19-May-11)