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DOI: 10.1160/TH10-09-0601
Rivaroxaban for the prevention of venous thromboembolism after hip or knee arthroplasty
Pooled analysis of four studiesPublikationsverlauf
Received:
27. September 2010
Accepted after minor revision:
25. November 2010
Publikationsdatum:
27. November 2017 (online)
![](https://www.thieme-connect.de/media/10.1055-s-00035024/201103/lookinside/thumbnails/10-1160-th10-09-0601-1.jpg)
Summary
Four phase III studies compared oral rivaroxaban with subcutaneous enoxaparin for the prevention of venous thromboembolism (VTE) after total hip or knee arthroplasty (THA or TKA). A pooled analysis of these studies compared the effect of rivaroxaban with enoxaparin on symptomatic VTE plus all-cause mortality and bleeding events, and determined whether these effects were consistent in patient subgroups. Patients (N=12,729) aged ≥18 years and scheduled for elective THA or TKA received rivaroxaban 10 mg once daily or enoxaparin 40 mg once daily or 30 mg every 12 hours. The composite of symptomatic VTE and all-cause mortality, the prespecified primary efficacy endpoint and adjudicated bleeding events were analysed in the day 12 ± 2 active treatment pool. Subgroup analyses of these outcomes were performed over the total treatment period. In the day 12 ± 2 pool, the primary efficacy endpoint occurred in 29/6,183 patients receiving rivaroxaban (0.5%) versus 60/6,200 patients receiving enoxaparin (1.0%; p=0.001). Major bleeding occurred in 21 (0.3%) versus 13 (0.2%) patients, p=0.23; major plus non-major clinically relevant bleeding in 176 (2.8%) versus 152 (2.5%) patients, p=0.19; and any bleeding in 409 (6.6%) versus 384 (6.2%) patients, p=0.38, respectively. The reduction of symptomatic VTE plus all-cause mortality was consistent across prespecified subgroups (age, gender, body weight, creatinine clearance) in the total treatment period. Compared with enoxaparin regimens, rivaroxaban reduces the composite of symptomatic VTE and all-cause mortality after elective THA or TKA, with a small increase in bleeding, no signs of compromised liver safety and fewer serious adverse events.
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References
- 1 Kakkar VV, Corrigan TP, Fossard DP. Prevention of fatal postoperative pulmonary embolism by low doses of heparin. An international multicentre trial. Lancet 1975; 2: 45-51.
- 2 Collins R, Scrimgeour A, Yusuf S. et al. Reduction in fatal pulmonary embolism and venous thrombosis by perioperative administration of subcutaneous heparin. Overview of results of randomized trials in general, orthopedic, and urologic surgery. N Engl J Med 1988; 318: 1162-1173.
- 3 Geerts WH, Bergqvist D, Pineo GF. et al. Prevention of venous thromboembolism: American College of Chest Physicians evidence-based clinical practice guidelines (8th Edition). Chest 2008; 133: 381S-453S.
- 4 Eriksson BI, Borris LC, Friedman RJ. et al. Rivaroxaban versus enoxaparin for thromboprophylaxis after hip arthroplasty. N Engl J Med 2008; 358: 2765-2775.
- 5 Kakkar AK, Brenner B, Dahl OE. et al. Extended duration rivaroxaban versus short-term enoxaparin for the prevention of venous thromboembolism after total hip arthroplasty: a double-blind, randomised controlled trial. Lancet 2008; 372: 31-39.
- 6 Lassen MR, Ageno W, Borris LC. et al. Rivaroxaban versus enoxaparin for thromboprophylaxis after total knee arthroplasty. N Engl J Med 2008; 358: 2776-2786.
- 7 Turpie AGG, Lassen MR, Davidson BL. et al. Rivaroxaban versus enoxaparin for thromboprophylaxis after total knee arthroplasty (RECORD4): a randomised trial. Lancet 2009; 373: 1673-1680.
- 8 Eriksson BI, Kakkar AK, Turpie AGG. et al. Oral rivaroxaban for the prevention of symptomatic venous thromboembolism after elective hip and knee replacement. J Bone Joint Surg Br 2009; 91: 636-644.
- 9 Schulman S, Kearon C. Definition of major bleeding in clinical investigations of antihemostatic medicinal products in non-surgical patients. J Thromb Haemost 2005; 3: 692-694.
- 10 European Medicines Agency – Committee for Medicinal Products for Human Use (CHMP).. Guideline on clinical investigation of medicinal products for prophylaxis of high intra- and post-operative venous thromboembolic risk. Available at: http://www.emea.europa.eu/pdfs/human/ewp/70798en_fin.pdf Accessed November 8, 2010.
- 11 DerSimonian R, Laird N. Meta-analysis in clinical trials. Control Clin Trials 1986; 7: 177-188.
- 12 Warwick D, Friedman RJ, Agnelli G. et al. Insufficient duration of venous thromboembolism prophylaxis after total hip or knee replacement when compared with the time course of thromboembolic events: findings from the Global Orthopaedic Registry. J Bone Joint Surg Br 2007; 89: 799-807.
- 13 Eriksson BI, Dahl OE, Rosencher N. et al. Dabigatran etexilate versus enoxaparin for prevention of venous thromboembolism after total hip replacement: a randomised, double-blind, non-inferiority trial. Lancet 2007; 370: 949-956.
- 14 Eriksson BI, Dahl OE, Rosencher N. et al. Oral dabigatran etexilate vs. subcutaneous enoxaparin for the prevention of venous thromboembolism after total knee replacement: the RE-MODEL randomized trial. J Thromb Haemost 2007; 5: 2178-2185.
- 15 The RE-MOBILIZE Writing Committee.. The oral thrombin inhibitor dabigatran etexilate vs the North American enoxaparin regimen for the prevention of venous thromboembolism after knee arthroplasty surgery. J Arthroplasty 2009; 24: 1-9.
- 16 Lassen MR, Raskob GE, Gallus A. et al. Apixaban or enoxaparin for thromboprophylaxis after knee replacement. N Engl J Med 2009; 361: 594-604.
- 17 Leclerc JR, Geerts WH, Desjardins L. et al. Prevention of deep vein thrombosis after major knee surgery–a randomized, double-blind trial comparing a low molecular weight heparin fragment (enoxaparin) to placebo. Thromb Haemost 1992; 67: 417-423.
- 18 Rosencher N, Kerkkamp HE, Macheras G. et al. Orthopedic Surgery Transfusion Hemoglobin European Overview (OSTHEO) study: blood management in elective knee and hip arthroplasty in Europe. Transfusion (Paris) 2003; 43: 459-469.
- 19 Turpie AG, Eriksson BI, Lassen MR. et al. A meta-analysis of fondaparinux versus enoxaparin in the prevention of venous thromboembolism after major orthopaedic surgery. J South Orthop Assoc 2002; 11: 182-188.