Elsevier

The Lancet

Volume 373, Issue 9676, 16–22 May 2009, Pages 1673-1680
The Lancet

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

https://doi.org/10.1016/S0140-6736(09)60734-0Get rights and content

Summary

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.

Introduction

The American College of Chest Physicians recommends prophylaxis for venous thromboembolism for at least 10 days after total knee arthroplasty (grade 1A recommendation).1 Given the trend for shorter hospital stays,2 a simple, effective, oral anticoagulant regimen for use in an outpatient setting would be beneficial. Rivaroxaban is a new oral agent that directly inhibits factor Xa, an enzyme of the coagulation cascade involved in the formation of thrombin.

RECORD4 (Regulation of Coagulation in Orthopaedic Surgery to Prevent Deep Vein Thrombosis and Pulmonary Embolism) is a multicentre, randomised, double-blind trial designed to assess the efficacy and safety of oral rivaroxaban 10 mg once daily compared with 30 mg enoxaparin given subcutaneously every 12 h, for the prevention of venous thromboembolism after elective total knee arthroplasty. RECORD4 differs from the previously reported RECORD trials,3, 4, 5 in comparing rivaroxaban with the 30 mg every 12 h enoxaparin regimen approved in North America for the prevention of venous thromboembolism after total knee arthroplasty.

Section snippets

Patients

Patients were eligible for the study if they were aged 18 years or older and were scheduled for total knee arthroplasty. Patients were excluded if they had active bleeding or a high risk of bleeding, or any disorder contraindicating the use of enoxaparin or that might necessitate enoxaparin dose adjustment. Other exclusion criteria included disorders preventing bilateral venography, clinically significant liver disease, severe renal impairment (creatinine clearance <30 mL per min), concomitant

Results

Between June, 2006, and October, 2007, 3418 patients were enrolled in 131 centres in 12 countries (figure), and of these, 3148 patients were randomly assigned treatment. 1742 patients were included in the per-protocol population, and 1924 in the modified intention-to-treat population. The reasons for exclusion from the various populations were similar in the rivaroxaban and enoxaparin groups (table 1). Proportions of patients with venograms adequate for assessment for the primary efficacy

Discussion

Oral, once-daily rivaroxaban 10 mg was more efficacious than subcutaneous enoxaparin 30 mg for the prevention of venous thromboembolism after total knee arthroplasty. Rivaroxaban significantly reduced the absolute risk of total venous thromboembolism by 3·2% (relative risk reduction 31%). Although there were more major, major plus clinically relevant non-major, and any bleeding events with rivaroxaban, the differences compared with enoxaparin were not statistically significant.

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