Skip to main content

Advertisement

SpringerLink
Log in

New oral anticoagulants: prevention of VTE in phase III studies in total joint replacement surgery and the hospitalized medically-ill patients

  • Published:
Journal of Thrombosis and Thrombolysis Aims and scope Submit manuscript

Abstract

Effective venous thromboembolism prophylaxis in hospitalized medically-ill patients and those undergoing orthopaedic surgery remains a challenge for clinicians in the United States. Several new oral anticoagulants, which either directly inhibit the activity of thrombin or factor Xa have been developed and studied for venous thromboembolism (VTE) prevention in phase III trials in these patient populations. These new medications demonstrate several advantages over traditional anticoagulants, including their administration at fixed doses with no requirement for routine coagulation monitoring. Such advantages may potentially be offset by the lack of well-studied methods to reverse their anticoagulant effects and the potential need for standardized testing to monitor their activity in certain situations. This review will provide an overview of the clinical trial results of dabigatran, apixaban and rivaroxaban for VTE prevention in the orthopaedic and medically-ill hospitalized patients.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

References

  1. Iorio R, Robb WJ, Healy WL et al (2008) Orthopaedic surgeon workforce and volume assessment for total hip and knee replacement in the United States: preparing for an epidemic. J Bone Joint Surg Am 90:1598–1605

    Article  PubMed  Google Scholar 

  2. Falck-Ytter Y, Francis CW, Johanson NA et al (2012) Prevention of VTE in orthopedic surgery patients: American college of Chest Physicians Evidence-based clinical practice guidelines (9th Edition). Chest 141:e278S–e325S

    Article  PubMed  CAS  Google Scholar 

  3. Geerts WH, Bergqvist D, Pineo GF et al (2008) Prevention of venous thromboembolism: american College of Chest Physicians evidence-based clinical practice guidelines (8th Edition). Chest 133:381S–453S

    Article  PubMed  CAS  Google Scholar 

  4. Anderson FA Jr, Spencer FA (2003) Risk factors for venous thromboembolism. Circulation 107:I9–I16

    Article  PubMed  Google Scholar 

  5. Ruppert A, Lees M, Steinle T (2010) Clinical burden of venous thromboembolism. Curr Med Res Opin 26:2465–2473

    Article  PubMed  Google Scholar 

  6. Pengo V, Lensing AW, Prins MH et al (2004) Incidence of chronic thromboembolic pulmonary hypertension after pulmonary embolism. N Engl J Med 350:2257–2264

    Article  PubMed  CAS  Google Scholar 

  7. Kachroo S, Boyd D, Bookhart B et al (2012) Quality of life and economic costs associtated with postthrombotic syndrome. Am J Heath Syst Pharm 69:567–572

    Article  Google Scholar 

  8. American Academy of Orthopaedic Surgeons. Preventing venous thromboembolic disease in patients undergoing elective hip and knee arthroplasty: evidence-based guidelines and evidence report. http://www.aaos.org/research/guidelines/VTE/VTE_full_guideline.pdf Accessed 15 Nov 2012

  9. Friedman RJ, Gallus A, Gil-Garay E, Fitzgerald G, Cushner F (2010) Practice patterns in the use of venous thromboembolism prophylaxis after total joint arthroplasty–insights from the Multinational Global Orthopaedic Registry (GLORY). Am J Orthop (Belle Mead NJ) 39:14–21

    Google Scholar 

  10. Eriksson BI, Dahl OE, Rosencher N et al (2007) Oral dabigatran etexilate vs. subcutaneous enoxaparin for the prevention of venous thromboembolism after total knee replacement: the RE-MODEL randomized trial. J Thromb Haemost 5:2178–2185

    Article  PubMed  CAS  Google Scholar 

  11. Ginsberg JS, Davidson BL, Comp PC et al (2009) Oral thrombin inhibitor dabigatran etexilate vs North American enoxaparin regimen for prevention of venous thromboembolism after knee arthroplasty surgery. J Arthroplast 24:1–9

    Google Scholar 

  12. Eriksson BI, Dahl OE, Rosencher N et al (2007) Dabigatran etexilate versus enoxaparin for prevention of venous thromboembolism after total hip replacement: a randomised, double-blind, non-inferiority trial. Lancet 370:949–956

    Article  PubMed  CAS  Google Scholar 

  13. Eriksson BI, Dahl OE, Huo MH et al (2011) Oral dabigatran versus enoxaparin for thromboprophylaxis after primary total hip arthroplasty (RE-NOVATE II). A randomised, double-blind, non-inferiority trial. Thromb Haemost 105:721–729

    Article  PubMed  CAS  Google Scholar 

  14. Lassen MR, Raskob GE, Gallus A et al (2009) Apixaban or enoxaparin for thromboprophylaxis after knee replacement. N Engl J Med 361:594–604

    Article  PubMed  CAS  Google Scholar 

  15. Lassen MR, Raskob GE, Gallus A et al (2010) Apixaban versus enoxaparin for thromboprophylaxis after knee replacement (ADVANCE-2): a randomised double-blind trial. Lancet 375:807–815

    Article  PubMed  CAS  Google Scholar 

  16. Lassen MR, Gallus A, Raskob GE et al (2010) Apixaban versus enoxaparin for thromboprophylaxis after hip replacement. N Engl J Med 363(2487–2498):25

    Google Scholar 

  17. Eriksson BI, Borris LC, Friedman RJ et al (2008) Rivaroxaban versus enoxaparin for thromboprophylaxis after hip arthroplasty. N Engl J Med 358:2765–2775

    Article  PubMed  CAS  Google Scholar 

  18. Kakkar AK, Brenner B, Dahl OE et al (2008) Extended duration rivaroxaban versus short-term enoxaparin for the prevention of venous thromboembolism after total hip arthroplasty: a double-blind, randomised controlled trial. Lancet 372:31–39

    Article  PubMed  CAS  Google Scholar 

  19. Lassen MR, Ageno W, Borris LC et al (2008) Rivaroxaban versus enoxaparin for thromboprophylaxis after total knee arthroplasty. N Engl J Med 358:2776–2786

    Article  PubMed  CAS  Google Scholar 

  20. Turpie AG, Lassen MR, Davidson BL et al (2009) Rivaroxaban versus enoxaparin for thromboprophylaxis after total knee arthroplasty (RECORD4): a randomised trial. Lancet 373:1673–1680

    Article  PubMed  CAS  Google Scholar 

  21. Cardiovascular and Renal Drugs Advisory Committee. FDA Advisory Committee Briefing Document. 2009. http://www.fda.gov/ohrms/dockets/ac/09/briefing/2009-4418b1-01-FDA.pdf. Accessed 15 Jan 2012

  22. Huisman MV, Quinlan DJ, Dahl OE, Shulman S (2010) Enoxaparin versus Dabigatran or rivaroxaban for thromboprophylaxis after hip or knee arthroplasty: results of separate pooled analysis of phase III multicenter randomized trials. Circ Cardiovasc Qual Outcomes 3:652–660

    Article  PubMed  Google Scholar 

  23. Turpie AG, Lassen MR, Eriksson BI et al (2011) Rivaroxaban for the prevention of venous thromboembolism after hip or knee arthroplasty. Pooled analysis of four studies. Thromb Haemost 105:444–453

    Article  PubMed  CAS  Google Scholar 

  24. Dabigatran [package insert EMEA], Germany, Boehringer Ingelheim Pharma 2012

  25. Apixaban [package insert EMEA], Italy, Bristol Myers Squibb, 2012

  26. Xarelto [package insert] Titusville, NJ: Janssen Pharmaceuticals, Inc, 2011

  27. Kahn SR, Panju A, Geerts W et al (2007) Multicenter evaluation of the use of venous Thromboembolism prophylaxis in acutely ill medical patients in Canada. Thromb Res 119:145–155

    Article  PubMed  CAS  Google Scholar 

  28. Tapson VF, Decousus H, Pini M et al (2007) Venous thromboembolism prophylaxis in acutely ill hospitalized medical patients: findings from the International Medical Prevention Registry on Venous Thromboembolism. Chest 132:936–945

    Article  PubMed  Google Scholar 

  29. Cohen AT, Tapson VF, Bergmann JF et al (2008) Venous Thromboembolism risk and prophylaxis in the acute hospital care setting (ENDORSE study): a multinational cross-sectional study. Lancet 371:387–394

    Article  PubMed  Google Scholar 

  30. Samama MM, Cohen AT, Darmon JY et al (1999) A comparison of enoxaparin with placebo for the prevention of venous thromboembolism in acutely ill medical patients. Prophylaxis in Medical Patients with Enoxaparin Study Group. N Engl J Med 341:793–800

    Article  PubMed  CAS  Google Scholar 

  31. Cohen AT, Davidson BL, Gallus AS et al (2006) Efficacy and safety of fondaparinux for the prevention of venous Thromboembolism in older acute medical patients: randomized placebo controlled trial. Br Med J 332:325–329

    Article  CAS  Google Scholar 

  32. Leizorovicz A, Cohen AT, Turpie AGG et al (2004) Randomized, placebo-controlled trial of dalteparin for the prevention of venous Thromboembolism in acutely ill medical patients. Circulation 110:874–879

    Article  PubMed  CAS  Google Scholar 

  33. Scannapieco G, Ageno W, Airoldit A et al (2010) Incidence and predictors of venous Thromboembolism in post acute care patients. A prospective cohort study. Thromb Haemost 104:734–740

    Article  PubMed  CAS  Google Scholar 

  34. Hull RD, Schellong SM, Tapson VF et al (2010) Extended duration venous thromboembolism prophylaxis in acutely ill medical patients with recently reduced mobility: a randomized trial. Ann Intern Med 153:8–18

    Article  PubMed  Google Scholar 

  35. Cohen AT, Spiro TE, Buller HR et al (2013) Rivaroxaban for thromboprophylaxis in acutely ill medical patients. N Engl J Med 368(6):513–523

    Article  PubMed  CAS  Google Scholar 

  36. Goldhaber SZ, Leizorovicz A, Kakkar AK et al (2011) Apixaban versus enoxaparin for thromboprophylaxis in medically ill patients. N Engl J Med 365:2167–2177

    Article  PubMed  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Jefferson Vascular Center, Jefferson Medical College, Thomas Jefferson University Hospitals, Gibbon Building, 111 South 11th Street, Suite 6270, Philadelphia, PA, USA

    Taki Galanis & Geno J. Merli

Authors
  1. Taki Galanis
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Geno J. Merli
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Geno J. Merli.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Galanis, T., Merli, G.J. New oral anticoagulants: prevention of VTE in phase III studies in total joint replacement surgery and the hospitalized medically-ill patients. J Thromb Thrombolysis 36, 141–148 (2013). https://doi.org/10.1007/s11239-013-0955-3

Download citation

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s11239-013-0955-3

Keywords

Search

Navigation