Edoxaban in the prevention and treatment of thromboembolic complications from a clinical point of view

Abstract

Edoxaban is an oral once-daily factor Xa inhibitor with a predictable anticoagulant effect. After oral administration, edoxaban is rapidly absorbed from the gastrointestinal tract, reaching the peak plasma concentrations at 1–2 h. Oral bioavailability is 62% in healthy subjects and the terminal half-life is approximately 10–14 h. Edoxaban has been extensively studied in three clinical scenarios. In ENGAGE AF-TIMI 48, edoxaban was at least as effective as warfarin, but with a marked lesser risk of bleeding. In the Hokusai-VTE study, edoxaban was as effective as warfarin for the prevention of recurrent venous thromboembolism (VTE) in patients with deep venous thrombosis, pulmonary embolism, or both, but with a lesser risk of bleeding. In the STARS program, edoxaban was more effective for the prevention of VTE after knee or hip arthroplasty than low-dose enoxaparin, without an increased bleeding risk. In this review, the available clinical evidence about edoxaban is updated.

Keywords:

• deep venous thrombosis
• direct oral anticoagulants
• edoxaban
• ENGAGE AF-TIMI 48
• hip arthroplasty
• Hokusai-VTE
• knee arthroplasty
• new oral anticoagulants
• non-valvular atrial fibrillation
• pulmonary embolism
• STARS program
• venous thromboembolism

Financial & competing interests disclosure

V Barrios has received honoraria for lectures from Boehringer Ingelheim, Bayer, BMS/Pfizer and Daiichi Sankyo and advisory board fees from Boehringer Ingelheim, Bayer and Daiichi Sankyo. C Escobar has received honoraria for lectures from Boehringer Ingelheim, Bayer, BMS/Pfizer and Daiichi Sankyo. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed. Editorial assistance was provided by Content Ed Net Communications, Madrid, Spain, in the production of this manuscript with funding from Daiichi Sankyo.

Key issues

• Vitamin K antagonists have been extensively used for the prevention and treatment of venous thromboembolism (VTE) and for the prevention of stroke in patients with atrial fibrillation (AF).

• Vitamin K antagonists have many disadvantages that limit their use in clinical practice.

• Edoxaban is an oral once-daily factor Xa inhibitor that overcomes these limitations.

• Edoxaban is the only once-daily oral direct anticoagulant specifically tested in Phase II clinical trials to find the most appropriate dose for AF patients.

• Once-daily regimens improve medication adherence compared with twice-daily regimens.

• The ENGAGE AF-TIMI 48 trial showed that both doses of edoxaban were at least as effective as warfarin in the prevention of stroke and systemic embolism. Both doses of edoxaban were associated with a lesser risk of bleeding (major bleeding, fatal bleeding, any intracranial bleeding, life-threatening bleeding and major or clinically relevant non-major bleeding).

• The STARS E-3 and STARS J-V trials showed that edoxaban was more effective for the prevention of DVT and PE after total knee or hip arthroplasty than low-dose enoxaparin, without an increase in the risk of bleeding.

• The Hokusai-VTE trial showed that edoxaban was as effective as warfarin for the prevention of recurrent VTE in patients with DVT, PE, or both, but with a lesser risk of major or clinically relevant non-major bleeding.

Notes