Skip to main content
Log in

Economic Evaluations of New Oral Anticoagulants for the Prevention of Venous Thromboembolism After Total Hip or Knee Replacement: A Systematic Review

  • Systematic Review
  • Published:
PharmacoEconomics Aims and scope Submit manuscript

Abstract

Background

Total hip replacement (THR) and total knee replacement (TKR) surgeries are being performed with increasing regularity and are associated with a high risk of developing a venous thromboembolism (VTE). New oral anticoagulants (NOACs) may be more effective at preventing VTEs but are associated with more bleeding events versus traditional anticoagulants.

Objective

The objective of this systematic review was to identify published economic analyses of NOACs for primary VTE prophylaxis following THR and TKR surgeries, and to summarise the modelling techniques used and the cost-effectiveness results.

Methods

Electronic searches of MEDLINE, EconLit and The Cochrane Library were performed from January 2008 to February 2015. Reference lists of included articles and reviews were examined for relevant studies.

Results

Sixteen relevant economic analyses were identified, all of which used decision-tree structures to model acute events after surgery; 13 included a chronic-phase Markov module to capture long-term complications of VTE and recurrent VTE events. All studies included prophylaxis-related major bleeding events and captured both symptomatic and asymptomatic VTE-related events; nine studies distinguished between distal and proximal deep vein thrombosis events. Overall, rivaroxaban dominated enoxaparin in eight of 11 studies and dalteparin in one study, dabigatran dominated enoxaparin in five of seven studies and apixaban dominated enoxaparin in two of two studies. Rivaroxaban dominated dabigatran in four of four studies, apixaban dominated dabigatran in two of two studies and rivaroxaban dominated apixaban in one study.

Conclusions

The economic analyses showed reasonable consistency in the model structures used and the events captured. The results strongly suggested that NOACs are cost effective alternatives to low molecular-weight heparin. Dabigatran appeared to be the least cost effective NOAC. More research is needed to assess the cost effectiveness of apixaban and edoxaban.

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

Access this article

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

Instant access to the full article PDF.

Fig. 1

Adapted from Moher et al. [9]

Fig. 2

aSources: [15, 19]. bSource: [19]. cSources: [19, 21]. dSources: [16, 17, 19, 20, 2224]. eSources: [11, 16, 17, 19, 22]. fThree separate analyses for France, Italy and Spain were conducted in one study [11]. gSources: [1014, 1619, 22, 25]. hSource: [10]

Similar content being viewed by others

References

  1. Derman PB, Fabricant PD, David G. The role of overweight and obesity in relation to the more rapid growth of total knee arthroplasty volume compared with total hip arthroplasty. J Bone Joint Surg. 2014;96(11):922–8.

    Article  PubMed  Google Scholar 

  2. Falck-Ytter Y, Francis CW, Johanson NA, Curley C, Dahl OE, Schulman S, American College of Chest Physicians, 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:e278S–325S.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  3. National Institute for Health and Care Excellence. Clinical guideline 92. Venous thromboembolism in adults admitted to hospital: reducing the risk. 2007. https://www.nice.org.uk/guidance/cg92. Accessed 10 Sept 2015.

  4. Adam SS, McDuffie JR, Lachiewicz PF, Ortel TL, Williams JW Jr. Comparative effectiveness of new oral anticoagulants and standard thromboprophylaxis in patients having total hip or knee replacement: a systematic review. Ann Intern Med. 2013;159(4):275–84.

    Article  PubMed  Google Scholar 

  5. Gómez-Outes A, Terleira-Fernández AI, Suárez-Gea ML, Vargas-Castrillón E. Dabigatran, rivaroxaban, or apixaban versus enoxaparin for thromboprophylaxis after total hip or knee replacement: systematic review, meta-analysis, and indirect treatment comparisons. BMJ. 2012;344:e3675.

    Article  PubMed  PubMed Central  Google Scholar 

  6. Wolowacz SE, Hess N, Brennan VK, Monz BU, Plumb JM. Cost-effectiveness of venous thromboembolism prophylaxis in total hip and knee replacement surgery: the evolving application of health economic modelling over 20 years. Curr Med Res Opin. 2008;24(10):2993–3006.

    Article  CAS  PubMed  Google Scholar 

  7. Siragusa S, Beltrametti C, Barone M, Piovella F. Clinical course and incidence of post-thrombophlebitic syndrome after profound asymptomatic deep vein thrombosis. Results of a transverse epidemiologic study [in Italian]. Minerva Cardioangiol. 1997;45:57–66.

    CAS  PubMed  Google Scholar 

  8. Kapoor A, Chuang W, Radhakrishnan N, Smith KJ, Berlowitz D, Segal JB, et al. Cost effectiveness of venous thromboembolism pharmacological prophylaxis in total hip and knee replacement: a systematic review. Pharmacoeconomics. 2010;28(7):521–38.

    Article  PubMed  PubMed Central  Google Scholar 

  9. Moher D, Liberati A, Tetzlaff J, Altman DG, The PRISMA Group. Preferred reporting items for systematic reviews and meta-analyses: the PRISMA statement. PLoS Med. 2009;6(7):e1000097.

    Article  PubMed  PubMed Central  Google Scholar 

  10. Ryttberg L, Diamantopoulos A, Forster F, Lees M, Fraschke A, Björholt I. Cost-effectiveness of rivaroxaban versus heparins for prevention of venous thromboembolism after total hip or knee surgery in Sweden. Expert Rev Pharmacoecon Outcomes Res. 2011;11(5):601–15.

    Article  PubMed  Google Scholar 

  11. Monreal M, Folkerts K, Diamantopoulos A, Imberti D, Brosa M. Cost-effectiveness impact of rivaroxaban versus new and existing prophylaxis for the prevention of venous thromboembolism after total hip or knee replacement surgery in France, Italy and Spain. Thromb Haemost. 2013;110(5):987–94.

    Article  CAS  PubMed  Google Scholar 

  12. Diamantopoulos A, Lees M, Wells PS, Forster F, Ananthapavan J, McDonald H. Cost-effectiveness of rivaroxaban versus enoxaparin for the prevention of postsurgical venous thromboembolism in Canada. Thromb Haemost. 2010;104(4):760–70.

    Article  CAS  PubMed  Google Scholar 

  13. Duran A, Sengupta N, Diamantopoulos A, Forster F, Kwong L, Lees M. Cost and outcomes associated with rivaroxaban vs enoxaparin for the prevention of postsurgical venous thromboembolism from a US payer’s perspective. J Med Econ. 2011;14(6):824–34.

    Article  PubMed  Google Scholar 

  14. Duran A, Sengupta N, Diamantopoulos A, Forster F, Kwong L, Lees M. Cost effectiveness of rivaroxaban versus enoxaparin for prevention of post-surgical venous thromboembolism from a US payer’s perspective. Pharmacoeconomics. 2012;30(2):87–101.

    Article  PubMed  Google Scholar 

  15. Gómez-Cerezo JF, Gómez-Arrayás I, Suárez-Fernández C, Betegón-Nicolás L, de Salas-Cansado M, Rubio-Terrés C. Cost-effectiveness analysis of apixaban compared to dabigatran in the prevention of venous thromboembolism in patients subjected to total knee or hip replacement [in Spanish]. Rev Esp Cir Ortop Traumatol. 2012;56(6):459–70.

    PubMed  Google Scholar 

  16. McCullagh L, Tilson L, Walsh C, Barry M. A cost-effectiveness model comparing rivaroxaban and dabigatran etexilate with enoxaparin sodium as thromboprophylaxis after total hip and total knee replacement in the Irish healthcare setting. Pharmacoeconomics. 2009;27(10):829–46.

    Article  PubMed  Google Scholar 

  17. McCullagh L, Walsh C, Barry M. Value-of-information analysis to reduce decision uncertainty associated with the choice of thromboprophylaxis after total hip replacement in the Irish healthcare setting. Pharmacoeconomics. 2012;30(10):941–59.

    Article  PubMed  Google Scholar 

  18. McDonald H, Diamantopoulos A, Wells P, Lees M, Folkerts K, Forster F, et al. Cost-effectiveness of rivaroxaban in the prevention of venous thromboembolism: a Canadian analysis using the Ontario Ministry of Health Perspective. J Med Econ. 2012;15(5):817–28.

    Article  PubMed  Google Scholar 

  19. Migliaccio-Walle K, Rublee D, Simon TA. Anticoagulation prophylaxis in orthopedic surgery: an efficiency frontier approach. Postgrad Med. 2012;124(1):41–9.

    Article  PubMed  Google Scholar 

  20. Omel’ianovskiĭ VV, Zagorodniĭ NV, Margieva AV, Tsfasman FM. Cost-effectiveness analysis of methods for thromboprophylaxis after orthopedic surgery [in Russian]. Khirurgiia (Mosk). 2010;5:72–81.

    Google Scholar 

  21. Revankar N, Patterson J, Kadambi A, Raymond V, El-Hadi W. A Canadian study of the cost-effectiveness of apixaban compared with enoxaparin for post-surgical venous thromboembolism prevention. Postgrad Med. 2013;125(4):141–53.

    Article  PubMed  Google Scholar 

  22. Ringerike T, Hamidi V, Hagen G, Reikvam A, Klemp M. Thromboprophylactic treatment with rivaroxaban or dabigatran compared with enoxaparin or dalteparin in patients undergoing elective hip- or knee replacement surgery. Report from Kunnskapssenteret (Norwegian Knowledge Centre for the Health Services) No. 13-2011. Health technology assessment (HTA) (medisinskmetodevurdering). 2011. http://hera.helsebiblioteket.no/hera/bitstream/10143/193189/1/NOKCrapport13_2011.pdf. Accessed 8 June 2015.

  23. Wolowacz SE, Roskell NS, Maciver F, Beard SM, Robinson PA, Plumb JM, et al. Economic evaluation of dabigatran etexilate for the prevention of venous thromboembolism after total knee and hip replacement surgery. Clin Ther. 2009;31(1):194–212.

    Article  PubMed  Google Scholar 

  24. Wolowacz SE, Roskell NS, Plumb JM, Clemens A, Noack H, Robinson PA, et al. Economic evaluation of dabigatran etexilate for the prevention of venous thromboembolism in patients aged over 75 years or with moderate renal impairment undergoing total knee or hip replacement. Thromb Haemost. 2010;103(2):360–71.

    Article  CAS  PubMed  Google Scholar 

  25. Zindel S, Stock S, Müller D, Stollenwerk B. A multi-perspective cost-effectiveness analysis comparing rivaroxaban with enoxaparin sodium for thromboprophylaxis after total hip and knee replacement in the German healthcare setting. BMC Health Serv Res. 2012;12:192.

    Article  PubMed  PubMed Central  Google Scholar 

  26. Pengo V, Lensing A, Prins M, Marchiori A, Davidson B, Tiozzo F, et al. Incidence of chronic thromboembolic pulmonary hypertension after pulmonary embolism. N Engl J Med. 2004;350:2257–64.

    Article  CAS  PubMed  Google Scholar 

  27. Eriksson BI, Borris LC, Friedman RJ, Haas S, Huisman MV, Kakkar AK, RECORD1 Study Group, et al. Rivaroxaban versus enoxaparin for thromboprophylaxis after hip arthroplasty. N Engl J Med. 2008;358:2765–75.

    Article  CAS  PubMed  Google Scholar 

  28. Kakkar AK, Brenner B, Dahl OE, Eriksson BI, Mouret P, Muntz J, RECORD2 Investigators, et al. Extended-duration rivaroxaban versus short-term enoxaparin for the prevention of venous thromboembolism after total hip arthroplasty: a double-blind, randomised controlled study. Lancet. 2008;372(9632):31–9.

    Article  CAS  PubMed  Google Scholar 

  29. Lassen MR, Ageno W, Borris LC, Lieberman JR, Rosencher N, Bandel TJ, RECORD3 Investigators, et al. Rivaroxaban versus enoxaparin for thromboprophylaxis after total knee arthroplasty. N Engl J Med. 2008;358:2776–86.

    Article  CAS  PubMed  Google Scholar 

  30. Eriksson BI, Dahl OE, Rosencher N, Kurth AA, van Dijk CN, Frostick SP, RE-MODEL Study Group, 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;5:2178–85.

    Article  CAS  PubMed  Google Scholar 

  31. Eriksson BI, Dahl OE, Rosencher N, Kurth AA, van Dijk CN, Frostick SP, RE-NOVATE Study Group, 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(9591):949–56.

    Article  CAS  PubMed  Google Scholar 

  32. Lassen MR, Gallus A, Raskob GE, Pineo G, Chen D, Ramirez LM, ADVANCE-3 Investigators. Apixaban versus enoxaparin for thromboprophylaxis after hip replacement. N Engl J Med. 2010;363:2487–98.

    Article  CAS  PubMed  Google Scholar 

  33. Lassen MR, Raskob GE, Gallus A, Pineo G, Chen D, Portman RJ. Apixaban or enoxaparin for thromboprophylaxis after knee replacement. N Engl J Med. 2009;361:594–604.

    Article  CAS  PubMed  Google Scholar 

  34. Lassen MR, Raskob GE, Gallus A, Pineo G, Chen D, Hornick D, ADVANCE-2 Investigators. Apixaban versus enoxaparin for thromboprophylaxis after knee replacement (ADVANCE-2): a randomised double-blind trial. Lancet. 2010;375:807–15.

    Article  CAS  PubMed  Google Scholar 

  35. Eriksson BI, Dahl OE, Huo MH, Kurth AA, Hantel S, Hermansson K, RE-NOVATE II Study Group, et al. Oral dabigatran versus enoxaparin for thromboprophylaxis after primary total hip arthroplasty (RE-NOVATE II). Thromb Haemost. 2011;105(4):721–9.

    Article  CAS  PubMed  Google Scholar 

Download references

Acknowledgements

James Brockbank and Sorrel Wolowacz are employees of RTI Health Solutions.

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to James Brockbank.

Ethics declarations

Conflicts of interest

James Brockbank and Sorrel Wolowacz are employees of RTI Health Solutions, a provider of research and consulting services to biopharmaceutical companies.

Funding

No sources of funding were received to conduct this research or prepare this manuscript.

Author contributions

Mr Brockbank and Dr Wolowacz contributed to the study design and preparation of the manuscript; Mr Brockbank performed the literature searches and data abstraction.

Electronic supplementary material

Below is the link to the electronic supplementary material.

Supplementary material 1 (DOCX 24 kb)

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Brockbank, J., Wolowacz, S. Economic Evaluations of New Oral Anticoagulants for the Prevention of Venous Thromboembolism After Total Hip or Knee Replacement: A Systematic Review. PharmacoEconomics 35, 517–535 (2017). https://doi.org/10.1007/s40273-017-0486-4

Download citation

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s40273-017-0486-4

Navigation