A once-daily, oral, direct Factor Xa inhibitor, rivaroxaban (BAY 59-7939), for thromboprophylaxis after total hip replacement.
BACKGROUND
Rivaroxaban (BAY 59-7939)--an oral, direct Factor Xa inhibitor--could be an alternative to heparins and warfarin for the prevention and treatment of thromboembolic disorders.


RESULTS
This randomized, double-blind, double-dummy, active-comparator-controlled, multinational, dose-ranging study assessed the efficacy and safety of once-daily rivaroxaban relative to enoxaparin for prevention of venous thromboembolism in patients undergoing elective total hip replacement. Patients (n=873) were randomized to once-daily oral rivaroxaban doses of 5, 10, 20, 30, or 40 mg (initiated 6 to 8 hours after surgery) or a once-daily subcutaneous enoxaparin dose of 40 mg (given the evening before and > or = 6 hours after surgery). Study drugs were continued for an additional 5 to 9 days; mandatory bilateral venography was performed the following day. The primary end point (composite of any deep vein thrombosis, objectively confirmed pulmonary embolism, and all-cause mortality) was observed in 14.9%, 10.6%, 8.5%, 13.5%, 6.4%, and 25.2% of patients receiving 5, 10, 20, 30, and 40 mg rivaroxaban, and 40 mg enoxaparin, respectively (n=618, per-protocol population). No significant dose-response relationship was found for efficacy (P=0.0852). Major postoperative bleeding was observed in 2.3%, 0.7%, 4.3%, 4.9%, 5.1%, and 1.9% of patients receiving 5, 10, 20, 30, and 40 mg rivaroxaban, and 40 mg enoxaparin, respectively (n=845, safety population), representing a significant dose-response relationship (P=0.0391).


CONCLUSIONS
Rivaroxaban showed efficacy and safety similar to enoxaparin for thromboprophylaxis after total hip replacement, with the convenience of once-daily oral dosing and without the need for coagulation monitoring. When both efficacy and safety are considered, these results suggest that 10 mg rivaroxaban once daily should be investigated in phase III studies.
Eriksson
Bengt I
BI
Department of Orthopaedics, Sahlgrenska University Hospital/Ostra, SE-416 85 Gothenburg, Sweden. b.eriksson@orthop.gu.se
Borris
Lars C
LC
Dahl
Ola E
OE
Haas
Sylvia
S
Huisman
Menno V
MV
Kakkar
Ajay K
AK
Muehlhofer
Eva
E
Dierig
Christoph
C
Misselwitz
Frank
F
Kälebo
Peter
P
D000284:Administration, Oral; D000328:Adult; D000925:Anticoagulants / Q000008:administration & dosage / Q000627:therapeutic use*; D019644:Arthroplasty, Replacement, Hip / Q000401:mortality; D004311:Double-Blind Method; D004334:Drug Administration Schedule; D065427:Factor Xa Inhibitors; D005260:Female; D006470:Hemorrhage / Q000517:prevention & control*; D006801:Humans; D008297:Male; D008875:Middle Aged; D009025:Morpholines / Q000008:administration & dosage / Q000627:therapeutic use*; D017698:Postmenopause; D011183:Postoperative Complications / Q000517:prevention & control*; D000069552:Rivaroxaban; D012449:Safety; D018401:Sample Size; D016019:Survival Analysis; D013876:Thiophenes / Q000008:administration & dosage / Q000627:therapeutic use*
D000925:Anticoagulants; D065427:Factor Xa Inhibitors; D009025:Morpholines; D013876:Thiophenes; D000069552:Rivaroxaban