FREE NEJM E-TOC    HOME   |   SUBSCRIBE   |   CURRENT ISSUE   |   PAST ISSUES   |   COLLECTIONS   |   Search Term  Advanced Search

Sign in | Get NEJM's E-Mail Table of Contents — Free | Subscribe

Previous Volume 358:2765-2775 June 26, 2008 Number 26 Next

	Full Text PDF PDA Full Text PowerPoint Slide Set CME Exam Supplementary Material Editorial by Lohrmann, J. Letters Add to Personal Archive Add to Citation Manager Notify a Friend E-mail When Cited E-mail When Letters Appear PubMed Citation

ABSTRACT

Background This phase 3 trial compared the efficacy and safety of rivaroxaban, an oral direct inhibitor of factor Xa, with those of enoxaparin for extended thromboprophylaxis in patients undergoing total hip arthroplasty.

Methods In this randomized, double-blind study, we assigned 4541 patients to receive either 10 mg of oral rivaroxaban once daily, beginning after surgery, or 40 mg of enoxaparin subcutaneously once daily, beginning the evening before surgery, plus a placebo tablet or injection. The primary efficacy outcome was the composite of deep-vein thrombosis (either symptomatic or detected by bilateral venography if the patient was asymptomatic), nonfatal pulmonary embolism, or death from any cause at 36 days (range, 30 to 42). The main secondary efficacy outcome was major venous thromboembolism (proximal deep-vein thrombosis, nonfatal pulmonary embolism, or death from venous thromboembolism). The primary safety outcome was major bleeding.

Results A total of 3153 patients were included in the superiority analysis (after 1388 exclusions), and 4433 were included in the safety analysis (after 108 exclusions). The primary efficacy outcome occurred in 18 of 1595 patients (1.1%) in the rivaroxaban group and in 58 of 1558 patients (3.7%) in the enoxaparin group (absolute risk reduction, 2.6%; 95% confidence interval [CI], 1.5 to 3.7; P<0.001). Major venous thromboembolism occurred in 4 of 1686 patients (0.2%) in the rivaroxaban group and in 33 of 1678 patients (2.0%) in the enoxaparin group (absolute risk reduction, 1.7%; 95% CI, 1.0 to 2.5; P<0.001). Major bleeding occurred in 6 of 2209 patients (0.3%) in the rivaroxaban group and in 2 of 2224 patients (0.1%) in the enoxaparin group (P=0.18).

Conclusions A once-daily, 10-mg oral dose of rivaroxaban was significantly more effective for extended thromboprophylaxis than a once-daily, 40-mg subcutaneous dose of enoxaparin in patients undergoing elective total hip arthroplasty. The two drugs had similar safety profiles. (ClinicalTrials.gov number, NCT00329628 [ClinicalTrials.gov] .)

Source Information

From Sahlgrenska University Hospital–Östra, Gothenburg, Sweden (B.I.E.); Aarhus University Hospital, Aarhus, Denmark (L.C.B.); Medical University of South Carolina, Charleston (R.J.F.); Institute of Experimental Oncology and Therapy Research, Technical University of Munich, Munich, Germany (S.H.); Leiden University Medical Center, Leiden, the Netherlands (M.V.H.); Thrombosis Research Institute, and Barts and the London School of Medicine, London (A.K.K.); Bayer HealthCare, Wuppertal, Germany (T.J.B., H.B., E.M., F.M.); and University of Toronto, Toronto (W.G.).

Address reprint requests to Dr. Eriksson at the Orthopedic Department, Sahlgrenska University Hospital–Östra, Smorslottsgatan 1, SE-41685 Gothenburg, Sweden, or at b.eriksson{at}orthop.gu.se.

Full Text of this Article

Related Letters:

Rivaroxaban for Thromboprophylaxis
Schuman E. P., Lippi G., Franchini M., Targher G., Lotke P. A., ten Cate H., Hamulyak K., Geerts W., the RECORD 1 and RECORD 3 Investigators , Lassen M. R., Ageno W., Turpie A. G.G., Lohrmann J., Becker R. C.
Extract | Full Text | PDF  
N Engl J Med 2008; 359:2174-2176, Nov 13, 2008. Correspondence

This article has been cited by other articles:

• Schulman, S. (2009). Rivaroxaban in Orthopedic Surgery -- A Change of Paradigm?. CLIN APPL THROMB HEMOST 15: 613-620 [Abstract]  
• Levine, M. N. (2009). New Antithrombotic Drugs: Potential for Use in Oncology. JCO 27: 4912-4918 [Abstract] [Full Text]  
• (2009). Anticoagulation with {blacktriangledown}dabigatran or{blacktriangledown}rivaroxaban. DTB 47: 116-120 [Abstract] [Full Text]  
• Calfon, M., Seddighzadeh, A., Piazza, G., Goldhaber, S. Z. (2009). Deep Vein Thrombosis in Orthopedic Surgery. CLIN APPL THROMB HEMOST 15: 512-516 [Abstract]  
• Lassen, M. R., Raskob, G. E., Gallus, A., Pineo, G., Chen, D., Portman, R. J. (2009). Apixaban or Enoxaparin for Thromboprophylaxis after Knee Replacement. NEJM 361: 594-604 [Abstract] [Full Text]  
• Van Thiel, D., Kalodiki, E., Wahi, R., Litinas, E., Haque, W., Rao, G. (2009). Interpretation of Benefit-Risk of Enoxaparin as Comparator in the RECORD Program: Rivaroxaban Oral Tablets (10 milligrams) for Use in Prophylaxis in Deep Vein Thrombosis and Pulmonary Embolism in Patients Undergoing Hip or Knee Replacement Surgery. CLIN APPL THROMB HEMOST 15: 389-394 [Abstract]  
• Hull, R. D., Yusen, R. D., Bergqvist, D. (2009). State-of-the-Art Review: Assessing the Safety Profiles of New Anticoagulants for Major Orthopedic Surgery Thromboprophylaxis. CLIN APPL THROMB HEMOST 15: 377-388 [Abstract]  
• Rajesparan, K., Biant, L. C., Ahmad, M., Field, R. E. (2009). The effect of an intravenous bolus of tranexamic acid on blood loss in total hip replacement. J Bone Joint Surg Br 91-B: 776-783 [Abstract] [Full Text]  
• Rea, C., Hunt, B. J (2009). Reducing vascular risk - venous thromboembolism and anticoagulation. Clin Risk 15: 90-92 [Full Text]  
• Eriksson, B. I., Kakkar, A. K., Turpie, A. G. G., Gent, M., Bandel, T.-J., Homering, M., Misselwitz, F., Lassen, M. R. (2009). Oral rivaroxaban for the prevention of symptomatic venous thromboembolism after elective hip and knee replacement. J Bone Joint Surg Br 91-B: 636-644 [Abstract] [Full Text]  
• Streiff, M. B., Haut, E. R. (2009). The CMS Ruling on Venous Thromboembolism After Total Knee or Hip Arthroplasty: Weighing Risks and Benefits. JAMA 301: 1063-1065 [Full Text]  
• Eikelboom, J. W., Karthikeyan, G., Fagel, N., Hirsh, J. (2009). American Association of Orthopedic Surgeons and American College of Chest Physicians Guidelines for Venous Thromboembolism Prevention in Hip and Knee Arthroplasty Differ: What Are the Implications for Clinicians and Patients?. Chest 135: 513-520 [Abstract] [Full Text]  
• Schuman, E. P., Lippi, G., Franchini, M., Targher, G., Lotke, P. A., ten Cate, H., Hamulyak, K., Geerts, W., the RECORD 1 and RECORD 3 Investigators, , Lassen, M. R., Ageno, W., Turpie, A. G.G., Lohrmann, J., Becker, R. C. (2008). Rivaroxaban for Thromboprophylaxis. NEJM 359: 2174-2176 [Full Text]  
• Buller, H. R., Lensing, A. W. A., Prins, M. H., Agnelli, G., Cohen, A., Gallus, A. S., Misselwitz, F., Raskob, G., Schellong, S., Segers, A., on behalf of the Einstein-DVT Dose-Ranging Study i, (2008). A dose-ranging study evaluating once-daily oral administration of the factor Xa inhibitor rivaroxaban in the treatment of patients with acute symptomatic deep vein thrombosis: the Einstein-DVT Dose-Ranging Study. Blood 112: 2242-2247 [Abstract] [Full Text]  
• (2008). All you need to read in the other general journals. BMJ 337: a582-a582 [Full Text]  
• (2008). Rivaroxaban Is Superior to Enoxaparin for Thromboprophylaxis After Knee and Hip Arthroplasty. JWatch General 2008: 1-1 [Full Text]  
• Lohrmann, J., Becker, R. C. (2008). New Anticoagulants -- The Path from Discovery to Clinical Practice. NEJM 358: 2827-2829 [Full Text]  
• (2008). Rivaroxaban for Thromboprophylaxis After Joint Replacement. JWatch Oncology and Hematology 2008: 1-1 [Full Text]  
• Francis, C. W. (2008). New Issues in Oral Anticoagulants. ASH Education Book 2008: 259-265 [Abstract] [Full Text]