Elsevier

The Lancet

Volume 372, Issue 9632, 5–11 July 2008, Pages 31-39
The Lancet

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Extended duration rivaroxaban versus short-term enoxaparin for the prevention of venous thromboembolism after total hip arthroplasty: a double-blind, randomised controlled trial

https://doi.org/10.1016/S0140-6736(08)60880-6Get rights and content

Summary

Background

The risk of venous thromboembolism is high after total hip arthroplasty and could persist after hospital discharge. Our aim was to compare the use of rivaroxaban for extended thromboprophylaxis with short-term thromboprophylaxis with enoxaparin.

Methods

2509 patients scheduled to undergo elective total hip arthroplasty were randomly assigned, stratified according to centre, with a computer-generated randomisation code, to receive oral rivaroxaban 10 mg once daily for 31–39 days (with placebo injection for 10–14 days; n=1252), or enoxaparin 40 mg once daily subcutaneously for 10–14 days (with placebo tablet for 31–39 days; n=1257). The primary efficacy outcome was the composite of deep-vein thrombosis (symptomatic or asymptomatic detected by mandatory, bilateral venography), non-fatal pulmonary embolism, and all-cause mortality up to day 30–42. Analyses were done in the modified intention-to-treat population, which consisted of all patients who had received at least one dose of study medication, had undergone planned surgery, and had adequate assessment of thromboembolism. This study is registered at ClinicalTrials.gov, number NCT00332020.

Findings

The modified intention-to-treat population for the analysis of the primary efficacy outcome consisted of 864 patients in the rivaroxaban group and 869 in the enoxaparin group. The primary outcome occurred in 17 (2·0%) patients in the rivaroxaban group, compared with 81 (9·3%) in the enoxaparin group (absolute risk reduction 7·3%, 95% CI 5·2–9·4; p<0·0001). The incidence of any on-treatment bleeding was much the same in both groups (81 [6·6%] events in 1228 patients in the rivaroxaban safety population vs 68 [5·5%] of 1229 patients in the enoxaparin safety population; p=0·25).

Interpretation

Extended thromboprophylaxis with rivaroxaban was significantly more effective than short-term enoxaparin plus placebo for the prevention of venous thromboembolism, including symptomatic events, in patients undergoing total hip arthroplasty.

Funding

Bayer HealthCare AG, Johnson & Johnson Pharmaceutical Research and Development LLC.

Introduction

Heparin-based thromboprophylaxis in the perioperative period reduces fatal pulmonary embolism.1 Its provision for the duration of hospital stay has been recommended for more than two decades,2 and its use is one of the most highly rated patient safety interventions.3 For patients undergoing elective hip arthroplasty, consensus guidelines recommend pharmacological prophylaxis for a minimum of 10 days, and up to 35 days after surgery.4, 5, 6 Despite evidence from meta-analyses indicating that extended thromboprophylaxis after elective hip arthroplasty reduces the frequency of venous thromboembolic disease,7, 8 its use out of hospital is infrequent, with less than 50% of patients receiving prophylaxis for 28 days in a large prospective registry.9 Alternative pharmacological methods include acetylsalicylic acid which, when used as extended thromboprophylaxis in a large trial,10 reduced the risk of pulmonary embolism and deep-vein thrombosis compared with placebo, although its use remains controversial in this setting.4, 5 Physicians have remained sceptical about the clinical relevance of extended prophylaxis, and are concerned about the potential risk for adverse outcomes, in particular bleeding.11

Trials of sufficient magnitude to show a consistent benefit for extending the duration of thromboprophylaxis, in terms of asymptomatic and symptomatic venous thromboembolism, with rigorous assessment of potential adverse events, are still required if the potential benefits of such interventions are to be more widely realised.12, 13, 14 Furthermore, the duration of short-term prophylaxis in existing trials has been suggested to be too short (7–10 days), and that trials comparing 10–14 days' prophylaxis with 28–35 days' prophylaxis and assessing symptomatic events would provide more valuable information.15 The aim of RECORD2 (REgulation of Coagulation in ORthopaedic surgery to prevent Deep-vein thrombosis and pulmonary embolism 2) was to assess extended thromboprophylaxis with an oral factor Xa inhibitor, rivaroxaban, for 31–39 days,16, 17, 18 compared with a short-term enoxaparin regimen for 10–14 days followed by placebo in patients undergoing total hip arthroplasty.

Section snippets

Patients

Patients were enrolled between February, 2006, and April, 2007, in this randomised, multinational, double-blind, double-dummy trial, involving 123 centres across 21 countries worldwide. Patients, aged 18 years or over, who were scheduled to undergo elective total hip arthroplasty were eligible for inclusion. Patients were ineligible if they were scheduled to undergo staged bilateral hip arthroplasty, had active bleeding or a high risk of bleeding, or had any condition contraindicating the use

Results

The trial profile is shown in figure 1. 776 patients were excluded from the modified intention-to-treat population for the primary efficacy analysis, and 52 patients were excluded from the safety population. Reasons for exclusion from the various study populations are shown in table 1. Baseline and surgical characteristics were much the same in the two groups (table 2). Mean duration of rivaroxaban therapy was 33·5 (SD 6·9) days, and 12·4 (3·0) days with enoxaparin (safety population).

The

Discussion

This trial indicates that extended thromboprophylaxis with rivaroxaban is significantly more effective than short-term thromboprophylaxis with enoxaparin followed by placebo for the prevention of venous thromboembolism—a composite of deep-vein thrombosis, non-fatal pulmonary embolism, and all-cause mortality—in patients undergoing total hip arthroplasty.

Current guidelines for extended prophylaxis after total hip arthroplasty are based on individual trials8, 20, 21, 22, 23, 24, 25, 26 that show

References (31)

  • Prevention of venous thrombosis and pulmonary embolism

    NIH consensus statement

    (1986)
  • KG Shojania et al.

    Making health care safer: a critical analysis of patient safety practices

  • Prophylaxis of venous thromboembolism. A national clinical guideline

    (2002)
  • Venous thromboembolism: reducing the risk of venous thromboembolism (deep vein thrombosis and pulmonary embolism) in inpatients undergoing surgery. NICE clinical guidelines

  • RD Hull et al.

    Extended out-of-hospital low-molecular-weight heparin prophylaxis against deep venous thrombosis in patients after elective hip arthroplasty: a systematic review

    Ann Intern Med

    (2001)
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