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Thromb Haemost 2013; 109(01): 154-163
DOI: 10.1160/TH12-07-0510
New Technologies, Diagnostic Tools and Drugs
Schattauer GmbH

Efficacy and safety of thromboprophylaxis with low-molecular-weight heparin or rivaroxaban in hip and knee replacement surgery

Findings from the ORTHO-TEP registry
Jan Beyer-Westendorf
1   Center for Vascular Medicine and Department of Medicine III, Division of Angiology, University Hospital “Carl Gustav Carus” Dresden, Dresden, Germany
,
Jörg Lützner
2   Clinic of Orthopaedic Surgery, University Hospital “Carl Gustav Carus” Dresden, Dresden, Germany
,
Lars Donath
1   Center for Vascular Medicine and Department of Medicine III, Division of Angiology, University Hospital “Carl Gustav Carus” Dresden, Dresden, Germany
,
Luise Tittl
1   Center for Vascular Medicine and Department of Medicine III, Division of Angiology, University Hospital “Carl Gustav Carus” Dresden, Dresden, Germany
,
Holger Knoth
3   Pharmacy Department, University Hospital “Carl Gustav Carus” Dresden, Dresden, Germany
,
Oliver C. Radke
3   Pharmacy Department, University Hospital “Carl Gustav Carus” Dresden, Dresden, Germany
,
Eberhard Kuhlisch
5   Institute for Medical Informatics and Biometry, Technical University Dresden, Germany
,
Thoralf Stange
5   Institute for Medical Informatics and Biometry, Technical University Dresden, Germany
,
Albrecht Hartmann
2   Clinic of Orthopaedic Surgery, University Hospital “Carl Gustav Carus” Dresden, Dresden, Germany
,
Klaus-Peter Günther
2   Clinic of Orthopaedic Surgery, University Hospital “Carl Gustav Carus” Dresden, Dresden, Germany
,
Norbert Weiss
1   Center for Vascular Medicine and Department of Medicine III, Division of Angiology, University Hospital “Carl Gustav Carus” Dresden, Dresden, Germany
,
Sebastian Werth
1   Center for Vascular Medicine and Department of Medicine III, Division of Angiology, University Hospital “Carl Gustav Carus” Dresden, Dresden, Germany
› Author Affiliations Financial support: The Ortho-TEP registry was partially supported by a grant of Bayer Healthcare, providing funding for a documentation assistant. The authors declare that the sponsor had no influence on the conduct of the study, data collection, statistical analysis or written presentation of study findings.
Further Information

Publication History

Received: 24 July 2012

Accepted after major revision: 01 October 2012

Publication Date:
25 November 2017 (online)

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Summary

Prospective trials have shown that rivaroxaban thromboprophylaxis is superior over low-molecular-weight heparin (LMWH) in patients undergoing hip and knee replacement surgery. However, patients treated under trial conditions are different from unselected routine patients, which may affect efficacy and safety of thromboprophylaxis. The objective was to evaluate the efficacy and safety of rivaroxaban or LMWH thromboprophylaxis in unselected patients undergoing hip and knee replacement surgery in daily care. In a monocentric, retrospective cohort study in 5,061 consecutive patients undergoing hip and knee replacement surgery a comparison of LMWH (hospital standard in 2006–2007) and rivaroxaban (since 2009) was made with regard to rates of symptomatic VTE, bleeding and surgical complications and length of hospital stay. Rates of symptomatic VTE were 4.1 % (LMWH) and 2.1 % (rivaroxaban; p=0.005) with rates for distal DVT 2.5 vs. 1.1 % (p<0.001). Rates of major VTE were numerically higher with LMWH (1.7 vs. 1.1%, not statistically significant). Rates of major bleeding (overt bleeding leading to surgical revision or death, occurring in a critical site, or transfusion of at least two units of packed red blood cells) were statistically lower with rivaroxaban (2.9 vs. 7.0%; p<0.001). Rivaroxaban patients had fewer surgical complications (1.1 vs. 3.7%; p<0.001) and a shorter length of hospitalisation (8.3 days; 95% CI 8.1– 8.5 vs. 11.1 days; 10.7– 11.5; p< 0.001). We conclude that rivaroxaban thromboprophylaxis is more effective than LMWH in unselected patients undergoing hip and knee replacement surgery in daily care and that switching from LMWH to rivaroxaban could be beneficial. Prospective comparisons are warranted to confirm our findings.

Keywords

Low-molecular-weight heparin - major orthopaedic surgery - rivaroxaban - venous thromboembolism - VTE prophylaxis
 

  • References

  • 1 Nicolaides AN, Breddin HK, Fareed J. et al. Prevention of venous thromboembolism. International Consensus Statement. Guidelines compiled in accordance with the scientific evidence. Int Angiol 2001; 20: 1-37. DOI:10.1177/000331970105200101.
    PubMedGoogle Scholar
  • 2 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 (06) 381S-453S. DOI:10.1378/chest.08-0656.
    CrossrefPubMedGoogle Scholar
  • 3 Falck-Ytter Y, Francis CW, Johanson NA. et al. Prevention of VTE in Orthopedic Surgery Patients: Antithrombotic Therapy and Prevention of Thrombosis, 9th ed: American College of Chest Physicians Evidence-Based Clinical Practice Guidelines. Chest 2012; 141 (02) e278S-325S. DOI:10.1378/chest.11-2404.
    CrossrefPubMedGoogle Scholar
  • 4 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. DOI:10.1302/0301-620X.89B6.18844.
    PubMedGoogle Scholar
  • 5 Wilke T, Moock J, Muller S. et al. Nonadherence in outpatient thrombosis prophylaxis with low molecular weight heparins after major orthopaedic surgery. Clin Orthop Relat Res 2010; 468: 2437-2453. DOI:10.1007/s11999-010-1306-8.
    CrossrefPubMedGoogle Scholar
  • 6 Eriksson BI, Borris LC, Friedman RJ. et al. Rivaroxaban versus enoxaparin for thromboprophylaxis after hip arthroplasty. N Engl J Med 2008; 358: 2765-2775. DOI:10.1056/NEJMoa0800374.
    CrossrefPubMedGoogle Scholar
  • 7 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. DOI:10.1056/NEJMoa076016.
    CrossrefPubMedGoogle Scholar
  • 8 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. DOI:10.1016/S0140-6736(08)60880-6.
    CrossrefPubMedGoogle Scholar
  • 9 Turpie AG, Lassen MR, Davidson BL. et al. Rivaroxaban versus enoxaparin for thromboprophylaxis after total knee arthroplasty (RECORD4): a randomised trial. Lancet 2009; 373: 1673-1680. DOI:10.1016/S0140-6736(09)60734-0.
    CrossrefPubMedGoogle Scholar
  • 10 Turpie AG, Lassen MR, Eriksson BI. et al. Rivaroxaban for the prevention of venous thromboembolism after hip or knee arthroplasty. Pooled analysis of four studies. Thromb Haemost 2011; 105: 444-453. DOI:10.1160/TH10-09-0601.
    Article in Thieme ConnectPubMedGoogle Scholar
  • 11 Rothwell PM. External validity of randomised controlled trials: „to whom do the results of this trial apply?. “ Lancet 2005; 365: 82-93. DOI:10.1016/S0140-6736(04)17670-8.
    PubMedGoogle Scholar
  • 12 Fortin M, Dionne J, Pinho G. et al. Randomized controlled trials: do they have external validity for patients with multiple comorbidities?. Ann Fam Med 2006; 04: 104-108. DOI:10.1370/afm.516.
    CrossrefPubMedGoogle Scholar
  • 13 Rosser WW. Application of evidence from randomised controlled trials to general practice. Lancet 1999; 353: 661-664. DOI:10.1016/S0140-6736(98)09103-X.
    CrossrefPubMedGoogle Scholar
  • 14 Donath L, Lutzner J, Werth S. et al. Efficacy and safety of venous thromboembolism prophylaxis with fondaparinux or low-molecular weight heparin in a large cohort of consecutive patients undergoing major orthopaedic surgery - findings from the ORTHO-TEP registry. Br J Clin Pharmacol. 2012 epub ahead of print
    PubMedGoogle Scholar
  • 15 Beyer-Westendorf J, Lutzner J, Donath L. et al. Efficacy and safety of rivaroxaban or fondaparinux thromboprophylaxis in major orthopaedic surgery - findings from the ortho-tep registry. J Thromb Haemost. 2012 epub ahead of print
    PubMedGoogle Scholar
  • 16 Schwarz T, Schmidt B, Schmidt B. et al. Interobserver agreement of complete compression ultrasound for clinically suspected deep vein thrombosis. Clin Appl Thromb Hemost 2002; 08: 45-49. DOI:10.1177/107602960200800106.
    CrossrefPubMedGoogle Scholar
  • 17 Schellong SM, Schwarz T, Halbritter K. et al. Complete compression ultrasonography of the leg veins as a single test for the diagnosis of deep vein thrombosis. Thromb Haemost 2003; 89: 228-234.
    Article in Thieme ConnectPubMedGoogle Scholar
  • 18 Schulman S, Kearon C. Definition of major bleeding in clinical investigations of antihemostatic medicinal products in non-surgical patients. J Thromb Haemost 2005; 03: 692-694. DOI:10.1111/j.1538-7836.2005.01204.x.
    CrossrefPubMedGoogle Scholar
  • 19 Schellong SM. Distal DVT: worth diagnosing? Yes. J Thromb Haemost 2007; 05 (Suppl. 01) 51-54. DOI:10.1111/j.1538-7836.2007.02490.x.
    CrossrefPubMedGoogle Scholar
  • 20 Righini M, Paris S, Le Gal G. et al. Clinical relevance of distal deep vein thrombosis. Review of literature data. Thromb Haemost 2006; 95: 56-64.
    Article in Thieme ConnectPubMedGoogle Scholar
  • 21 Seinturier C, Bosson JL, Colonna M. et al. Site and clinical outcome of deep vein thrombosis of the lower limbs: an epidemiological study. J Thromb Haemost 2005; 03: 1362-1367. DOI:10.1111/j.1538-7836.2005.01393.x.
    CrossrefPubMedGoogle Scholar
  • 22 Iskander GA, Nelson RS, Morehouse DL. et al. A: Incidence and propagation of infrageniculate deep venous thrombosis in trauma patients. J Trauma 2006; 61: 695-700. DOI:10.1097/01.ta.0000210453.70742.7f.
    CrossrefPubMedGoogle Scholar
  • 23 Chagnon I, Bounameaux H, Aujesky D. et al. Comparison of Two Clinical Prediction Rules and Implicit Assessment among Patients with Suspected Pulmonary Embolism. Am J Med 2002; 113: 269-275. DOI:10.1016/S0002-9343(02)01212-3.
    CrossrefPubMedGoogle Scholar
  • 24 Schiff RL, Kahn SR, Shrier I. et al. Identifying orthopedic patients at high risk for venous thromboembolism despite thromboprophylaxis. Chest 2005; 128: 3364-3371. DOI:10.1378/chest.128.5.3364.
    CrossrefPubMedGoogle Scholar
  • 25 Eriksson BI, Kakkar AK, Turpie AG. 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. DOI:10.1302/0301-620X.91B5.21691.
    PubMedGoogle Scholar
  • 26 Kistler U, Kramers-de Quervain I, Munzinger U. et al. Bleeding complications after systematic switch of routine thromboprophylaxis for major orthopaedic surgery. Thromb Haemost 2008; 99: 1049-1052.
    Article in Thieme ConnectPubMedGoogle Scholar