Rivaroxaban versus enoxaparin for thromboprophylaxis after total knee arthroplasty (RECORD4): a randomised trial.

Abstract

BACKGROUND:

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.

METHODS:

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.

FINDINGS:

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).

INTERPRETATION:

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.

FUNDING:

Bayer Schering Pharma AG, Johnson & Johnson Pharmaceutical Research & Development.

• Authors: Alexander G G Turpie, Michael R Lassen, Bruce L Davidson, Kenneth A Bauer, Michael Gent, Louis M Kwong, Fred D Cushner, Paul A Lotke, Scott D Berkowitz, Tiemo J Bandel, Alice Benson, Frank Misselwitz, William D Fisher, RECORD4 Investigators
• Journal: Lancet (London, England) (Lancet) Vol. 373 Issue 9676 Pg. 1673-80 (05 16 2009) ISSN: 1474-547X [Electronic] England
• PMID: 19411100 (Publication Type: Clinical Trial, Phase III, Comparative Study, Journal Article, Multicenter Study, Randomized Controlled Trial, Research Support, Non-U.S. Gov't)

Chemical References

• Anticoagulants
• Enoxaparin
• Morpholines
• Thiophenes
• Rivaroxaban

Topics

• Administration, Oral
• Aged
• Analysis of Variance
• Anticoagulants (therapeutic use)
• Arthroplasty, Replacement, Knee (adverse effects)
• Double-Blind Method
• Enoxaparin (therapeutic use)
• Female
• Follow-Up Studies
• Hemorrhage (chemically induced, epidemiology)
• Humans
• Incidence
• Male
• Middle Aged
• Morpholines (adverse effects, therapeutic use)
• Phlebography
• Risk Reduction Behavior
• Rivaroxaban
• Sensitivity and Specificity
• Thiophenes (adverse effects, therapeutic use)
• Treatment Outcome
• Venous Thrombosis (diagnostic imaging, epidemiology, etiology, prevention & control)