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