Summary
Edoxaban is a new oral direct factor Xa inhibitor. The purpose of this study was to
evaluate the efficacy and safety of different doses of edoxaban for the prevention
of venous thromboembolism (VTE) in patients undergoing elective total hip replacement.
A total of 903 patients were randomised to oral edoxaban 15, 30, 60 or 90 mg once
daily or subcutaneous dalteparin once daily (initial dose 2,500 IU, subsequent doses
5,000 IU). Both drugs were begun 6–8 hours postoperatively and continued for 7–10
days, when bilateral venography was performed. The primary efficacy endpoint was the
incidence of total VTE, which included proximal and/or distal deep-vein thrombosis
(DVT) by venography or symptomatic, objectively confirmed DVT or pulmonary embolism
during the treatment period. The primary safety outcome was the incidence of the composite
of major and clinically relevant non-major bleeding. All venograms and bleeding events
were reviewed by a central independent adjudication committee blinded as to treatment
allocation. Of the 903 patients randomised, 776 were evaluable for the primary efficacy
analysis. The incidences of VTE were 28.2%, 21.2%, 15.2%, and 10.6% in patients receiving
edoxaban 15, 30, 60 and 90 mg, respectively, compared with 43.8% in the dalteparin
group (p<0.005 ). There was a statistically significant (p<0.001) dose-response for
efficacy across the edoxaban dose groups for total VTE and for major VTE. The incidence
of clinically relevant bleeding was low and similar across the groups. Oral edoxaban
once daily is effective for preventing VTE after total hip replacement.
Keywords
Thromboprophylaxis - anticoagulant therapy - venous thromboembolism - factor Xa inhibitor
- edoxaban
