Oral direct factor Xa inhibition with edoxaban for thromboprophylaxis after elective total hip replacement. A randomised double-blind dose-response study.
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.
Raskob
Gary
G
College of Public Health, The University of Oklahoma Health Sciences Center, Oklahoma City, Oklahoma 73104, USA. Gary-Raskob@ouhsc.edu
Cohen
Alexander T
AT
Eriksson
Bengt I
BI
Puskas
David
D
Shi
Minggao
M
Bocanegra
Tomas
T
Weitz
Jeffrey I
JI
D000284:Administration, Oral; D000368:Aged; D000925:Anticoagulants / Q000008:administration & dosage* / Q000009:adverse effects; D019644:Arthroplasty, Replacement, Hip / Q000009:adverse effects; D002170:Canada; D017985:Dalteparin / Q000008:administration & dosage* / Q000009:adverse effects; D004311:Double-Blind Method; D004334:Drug Administration Schedule; D017558:Elective Surgical Procedures; D005060:Europe; D015951:Factor Xa / Q000378:metabolism; D065427:Factor Xa Inhibitors; D005260:Female; D005343:Fibrinolytic Agents / Q000008:administration & dosage* / Q000009:adverse effects; D006470:Hemorrhage / Q000139:chemically induced; D006801:Humans; D007279:Injections, Subcutaneous; D016015:Logistic Models; D008297:Male; D008875:Middle Aged; D010690:Phlebography; D011655:Pulmonary Embolism / Q000097:blood / Q000000981:diagnostic imaging / Q000209:etiology / Q000517:prevention & control*; D011725:Pyridines / Q000008:administration & dosage* / Q000009:adverse effects; D018570:Risk Assessment; D012307:Risk Factors; D013844:Thiazoles / Q000008:administration & dosage* / Q000009:adverse effects; D013997:Time Factors; D016896:Treatment Outcome; D014481:United States; D054556:Venous Thromboembolism / Q000097:blood / Q000000981:diagnostic imaging / Q000209:etiology / Q000517:prevention & control*; D020246:Venous Thrombosis / Q000097:blood / Q000000981:diagnostic imaging / Q000209:etiology / Q000517:prevention & control*
D000925:Anticoagulants; D065427:Factor Xa Inhibitors; D005343:Fibrinolytic Agents; D011725:Pyridines; D013844:Thiazoles; D015951:Factor Xa; C552171:edoxaban; D017985:Dalteparin