Edoxaban, a new oral direct factor Xa inhibitor, for non-valvular atrial fibrillation and symptomatic venous thromboembolism
Edoxaban is a once-daily oral anticoagulant that rapidly and selectively inhibits factor Xa in a concentration-dependent manner.
A review has described the extensive clinical development program of Edoxaban ( Lixiana in European Union ), including phase III studies in patients with non-valvular atrial fibrillation ( NVAF ) and symptomatic venous thromboembolism ( VTE ).
The ENGAGE AF-TIMI 48 study ( n= 21,105; mean CHADS2 score 2.8 ) compared Edoxaban 60 mg once daily ( high-dose regimen ) and Edoxaban 30 mg once daily ( low-dose regimen ) with dose-adjusted Warfarin ( Coumadin ) [ international normalized ratio ( INR ) 2.0–3.0 ] and found that both regimens were non-inferior to Warfarin in the prevention of stroke and systemic embolism in patients with NVAF.
Both Edoxaban regimens also provided significant reductions in the risk of hemorrhagic stroke, cardiovascular mortality, major bleeding and intracranial bleeding.
The Hokusai-VTE study ( n= 8,292 ) in patients with symptomatic venous thromboembolism had a flexible treatment duration of 3-12 months and found that following initial Heparin, Edoxaban 60 mg once daily was non-inferior to dose-adjusted Warfarin ( INR 2.0-3.0 ) for the prevention of recurrent venous thromboembolism, and also had a significantly lower risk of bleeding events.
Both studies randomized patients at moderate-to-high risk of thromboembolic events and were further designed to simulate routine clinical practice as much as possible, with Edoxaban dose reduction ( halving dose ) at randomisation or during the study if required, a frequently monitored and well-controlled Warfarin group, a well-monitored transition period at study end and a flexible treatment duration in Hokusai-VTE. ( Xagena )
Bounameaux H, Camm AJ, Drugs 2014; 74: 1209-1231