Rivaroxaban versus enoxaparin for thromboprophylaxis after total knee arthroplasty (RECORD4): a randomised trial.
Prophylaxis for venous thromboembolism is recommended for at least 10 days after total knee arthroplasty; oral regimens could enable shorter hospital stays. We aimed to test the efficacy and safety of oral rivaroxaban for the prevention of venous thromboembolism after total knee arthroplasty.



In a randomised, double-blind, phase III study, 3148 patients undergoing knee arthroplasty received either oral rivaroxaban 10 mg once daily, beginning 6-8 h after surgery, or subcutaneous enoxaparin 30 mg every 12 h, starting 12-24 h after surgery. Patients had mandatory bilateral venography between days 11 and 15. The primary efficacy outcome was the composite of any deep-vein thrombosis, non-fatal pulmonary embolism, or death from any cause up to day 17 after surgery. Efficacy was assessed as non-inferiority of rivaroxaban compared with enoxaparin in the per-protocol population (absolute non-inferiority limit -4%); if non-inferiority was shown, we assessed whether rivaroxaban had superior efficacy in the modified intention-to-treat population. The primary safety outcome was major bleeding. This trial is registered with ClinicalTrials.gov, number NCT00362232.



The primary efficacy outcome occurred in 67 (6.9%) of 965 patients given rivaroxaban and in 97 (10.1%) of 959 given enoxaparin (absolute risk reduction 3.19%, 95% CI 0.71-5.67; p=0.0118). Ten (0.7%) of 1526 patients given rivaroxaban and four (0.3%) of 1508 given enoxaparin had major bleeding (p=0.1096).



Oral rivaroxaban 10 mg once daily for 10-14 days was significantly superior to subcutaneous enoxaparin 30 mg given every 12 h for the prevention of venous thromboembolism after total knee arthroplasty.



Bayer Schering Pharma AG, Johnson & Johnson Pharmaceutical Research & Development.
McMaster University, Hamilton, Ontario L8L 2X2, Canada. turpiea@mcmaster.ca
Alexander G G
AG
Turpie
Michael R
MR
Lassen
Bruce L
BL
Davidson
Kenneth A
KA
Bauer
Michael
M
Gent
Louis M
LM
Kwong
Fred D
FD
Cushner
Paul A
PA
Lotke
Scott D
SD
Berkowitz
Tiemo J
TJ
Bandel
Alice
A
Benson
Frank
F
Misselwitz
William D
WD
Fisher
D000284:Administration, Oral; D000368:Aged; D000704:Analysis of Variance; D000925:Anticoagulants / Q000627:therapeutic use; D019645:Arthroplasty, Replacement, Knee / Q000009:adverse effects*; D004311:Double-Blind Method; D017984:Enoxaparin / Q000627:therapeutic use; D005260:Female; D005500:Follow-Up Studies; D006470:Hemorrhage / Q000139:chemically induced / Q000453:epidemiology; D006801:Humans; D015994:Incidence; D008297:Male; D008875:Middle Aged; D009025:Morpholines / Q000009:adverse effects / Q000627:therapeutic use*; D010690:Phlebography; D040242:Risk Reduction Behavior; D000069552:Rivaroxaban; D012680:Sensitivity and Specificity; D013876:Thiophenes / Q000009:adverse effects / Q000627:therapeutic use*; D016896:Treatment Outcome; D020246:Venous Thrombosis / Q000000981:diagnostic imaging / Q000453:epidemiology / Q000209:etiology / Q000517:prevention & control*
D000925:Anticoagulants; D017984:Enoxaparin; D009025:Morpholines; D013876:Thiophenes; D000069552:Rivaroxaban