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.