Skip to main content
SpringerLink
Log in

Cost Effectiveness of Apixaban and Enoxaparin for the Prevention of Venous Thromboembolism After Total Knee Replacement in China

  • Original Research Article
  • Published:
Clinical Drug Investigation Aims and scope Submit manuscript

Abstract

Background and Objectives

Apixaban and enoxaparin are indicated for preventing venous thromboembolism (VTE). The aim of this study was to evaluate the cost effectiveness of apixaban versus enoxaparin for the prophylaxis of VTE and associated long-term complications in Chinese patients after total knee replacement (TKR).

Methods

A decision model, which included both acute VTE (represented as a decision tree) and the long-term complications of VTE (represented as a Markov model), was developed to assess the economic outcomes of the two prophylactic strategies for Chinese patients after TKR. Transition probabilities, costs, and utilities were derived from published literature. One-way and probabilistic sensitivity analyses were performed to test the uncertainty concerning the model parameters. Quality-adjusted life-years (QALYs) and direct medical costs were reported over a 5-year horizon. Incremental cost-effectiveness ratios (ICERs) were also calculated.

Results

Thromboprophylaxis with apixaban was estimated to have a higher cost (US$68) and more health benefits (0.0006 QALYs) than thromboprophylaxis with enoxaparin over a 5.5-year time horizon, resulting in an ICER of US$108,497 per QALY gained. One-way sensitivity analyses found that the cost of apixaban and the probability of pulmonary embolism when taking either apixaban or enoxaparin had a considerable impact on the model outcomes.

Conclusions

Overall, the analysis found that the use of enoxaparin in Chinese patients after TKR was likely to be more cost effective than the use of apixaban.

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

Fig. 1
Fig. 2
Fig. 3

Similar content being viewed by others

References

  1. Turpie AGG, Bauer KA, Eriksson BI, Lassen MR, For the Steering Committess of the Pentasaccharide Orthopedic Prophylaxis Studies. Fondaparinux vs enoxaparin for the prevention of venous thromboembolism in major orthopedic surgery: a meta-analysis of 4 randomized double-blind studies. Arch Intern Med. 2002;162(16):1833–40.

    Article  CAS  PubMed  Google Scholar 

  2. Goldhaber SZ, Bounameaux H. Pulmonary embolism and deep vein thrombosis. Lancet. 2012;379(9828):1835–46.

    Article  PubMed  Google Scholar 

  3. Ruppert A, Steinle T, Lees M. Economic burden of venous thromboembolism: a systematic review. J Med Econ. 2011;14(1):65–74.

    Article  PubMed  Google Scholar 

  4. MacDougall DA, Feliu AL, Boccuzzi SJ, Lin J. Economic burden of deep-vein thrombosis, pulmonary embolism, and post-thrombotic syndrome. Am J Health Syst Pharm. 2006;63(20 Suppl 6):S5–15.

    Article  PubMed  Google Scholar 

  5. Geerts WH, Bergqvist D, Pineo GF, Heit JA, Samama CM, Lassen MR, et al. Prevention of venous thromboembolism. Chest. 2008;133(6):381S–453S.

    Article  CAS  PubMed  Google Scholar 

  6. Piovella F, Wang CJ, Lu H, Lee K, Lee LH, Lee WC, et al. Deep-vein thrombosis rates after major orthopedic surgery in Asia. An epidemiological study based on postoperative screening with centrally adjudicated bilateral venography. J Thromb Haemost. 2005;3(12):2664–70.

    Article  CAS  PubMed  Google Scholar 

  7. Chinese Orthopaedic Association. Guidelines for deep venous thrombosis prophylaxis during Orthopaedic surgery. Chin J Orthop. 2009;29(6):602–4.

    Google Scholar 

  8. Mandernach MW, Beyth RJ, Rajasekhar A. Apixaban for the prophylaxis and treatment of deep vein thrombosis and pulmonary embolism: an evidence-based review. Ther Clin Risk Manag. 2015;11:1273–82.

    Article  PubMed  PubMed Central  Google Scholar 

  9. Lassen MR, Gallus A, Raskob GE, Pineo G, Chen D, Ramirez LM, et al. Apixaban versus enoxaparin for thromboprophylaxis after hip replacement. N Engl J Med. 2010;363(26):2487–98.

    Article  CAS  PubMed  Google Scholar 

  10. Sullivan SD, Kahn SR, Davidson BL, Borris L, Bossuyt P, Raskob G. Measuring the outcomes and pharmacoeconomic consequences of venous thromboembolism prophylaxis in major orthopaedic surgery. Pharmacoeconomics. 2003;21(7):477–96.

    Article  PubMed  Google Scholar 

  11. 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 

  12. 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 

  13. Botteman MF, Caprini J, Stephens JM, Nadipelli V, Bell CF, Pashos CL, et al. Results of an economic model to assess the cost-effectiveness of enoxaparin, a low-molecular-weight heparin, versus warfarin for the prophylaxis of deep vein thrombosis and associated long-term complications in total hip replacement surgery in the United States. Clin Ther. 2002;24(11):1960–86 (discussion 38).

  14. Gordois A, Posnett J, Borris L, Bossuyt P, Jonsson B, Levy E, et al. The cost-effectiveness of fondaparinux compared with enoxaparin as prophylaxis against thromboembolism following major orthopedic surgery. J Thromb Haemost. 2003;1(10):2167–74.

    Article  CAS  PubMed  Google Scholar 

  15. Lagerstedt CI, Olsson CG, Fagher BO, Oqvist BW, Albrechtsson U. Need for long-term anticoagulant treatment in symptomatic calf-vein thrombosis. Lancet. 1985;2(8454):515–8.

    Article  CAS  PubMed  Google Scholar 

  16. Moser KM, LeMoine JR. Is embolic risk conditioned by location of deep venous thrombosis? Ann Intern Med. 1981;94(4 pt 1):439–44.

    Article  CAS  PubMed  Google Scholar 

  17. Task Group of the Chinese Guidelines for Pharmacoeconomic Evaluations. China guidelines for pharmacoeconomic evaluations. China J Pharm Econ. 2011;3:7–48.

  18. List of Chinese administrative divisions by GDP per capita. http://en.wikipedia.org/wiki/List_of_Chinese_administrative_divisions_by_GDP_per_capita. Accessed 28 Oct 2011.

  19. Eichler HG, Kong SX, Gerth WC, Mavros P, Jonsson B. Use of cost-effectiveness analysis in health-care resource allocation decision-making: how are cost-effectiveness thresholds expected to emerge? Value Health. 2004;7(5):518–28.

  20. Murray CJ, Evans DB, Acharya A, Baltussen RM. Development of WHO guidelines on generalized cost-effectiveness analysis. Health Econ. 2000;9(3):235–51.

    Article  CAS  PubMed  Google Scholar 

  21. Nakamura M, Miyata T, Ozeki Y, Takayama M, Komori K, Yamada N, et al. Current venous thromboembolism management and outcomes in Japan. Circ J. 2014;78(3):708–17.

    Article  PubMed  Google Scholar 

  22. Prandoni P, Villalta S, Bagatella P, Rossi L, Marchiori A, Piccioli A, et al. The clinical course of deep-vein thrombosis. Prospective long-term follow-up of 528 symptomatic patients. Haematologica. 1997;82(4):423–8.

  23. Nakamura M, Yamada N, Ito M. Current management of venous thromboembolism in Japan: current epidemiology and advances in anticoagulant therapy. J Cardiol. 2015;66(6):451–9.

    Article  PubMed  Google Scholar 

  24. Pengo V, Lensing AW, Prins MH, Marchiori A, Davidson BL, Tiozzo F, et al. Incidence of chronic thromboembolic pulmonary hypertension after pulmonary embolism. N Engl J Med. 2004;350(22):2257–64.

    Article  CAS  PubMed  Google Scholar 

  25. Life tables for WHO member states. http://www.who.int/gho/mortality_burden_disease/life_tables/life_tables/en/. Accessed 26 July 2016.

  26. 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 

  27. Oster G, Tuden RL, Colditz GA. A cost-effectiveness analysis of prophylaxis against deep-vein thrombosis in major orthopedic surgery. JAMA. 1987;257(2):203–8.

    Article  CAS  PubMed  Google Scholar 

  28. Menzin J, Colditz GA, Regan MM, Richner RE, Oster G. Cost-effectiveness of enoxaparin vs low-dose warfarin in the prevention of deep-vein thrombosis after total hip replacement surgery. Arch Intern Med. 1995;155(7):757–64.

    Article  CAS  PubMed  Google Scholar 

  29. Nerurkar J, Wade WE, Martin BC. Cost/death averted with venous thromboembolism prophylaxis in patients undergoing total knee replacement or knee arthroplasty. Pharmacotherapy. 2002;22(8):990–1000.

    Article  PubMed  Google Scholar 

  30. Rubinstein I, Murray D, Hoffstein V. Fatal pulmonary emboli in hospitalized patients. An autopsy study. Arch Intern Med. 1988;148(6):1425–6.

    Article  CAS  PubMed  Google Scholar 

  31. Douketis JD, Kearon C, Bates S, Duku EK, Ginsberg JS. Risk of fatal pulmonary embolism in patients with treated venous thromboembolism. JAMA. 1998;279(6):458–62.

    Article  CAS  PubMed  Google Scholar 

  32. Stein PD, Henry JW. Prevalence of acute pulmonary embolism among patients in a general hospital and at autopsy. Chest. 1995;108(4):978–81.

    Article  CAS  PubMed  Google Scholar 

  33. Hansson PO, Sorbo J, Eriksson H. Recurrent venous thromboembolism after deep vein thrombosis: incidence and risk factors. Arch Intern Med. 2000;160(6):769–74.

    Article  CAS  PubMed  Google Scholar 

  34. Heit JA, Rooke TW, Silverstein MD, Mohr DN, Lohse CM, Petterson TM, et al. Trends in the incidence of venous stasis syndrome and venous ulcer: a 25-year population-based study. J Vasc Surg. 2001;33(5):1022–7.

    Article  CAS  PubMed  Google Scholar 

  35. Bao L, Xiaoping X, Yue G, Zhengang C. Cost-effectiveness of apixaban compared with enoxaparin for prevention of venous thromboembolism after major orthopedic surgery in China. Chin J Jt Surg (Electronic Version). 2014;8(5):677–81.

    Google Scholar 

  36. Xu H, Zhang Y, Liu L, Zou R. Warfarin dosing and pharmacoeconomic evaluation in patients after mechanical prosthesis aortic valve replacement. Acta Academiae Medicinae Jiangxi. 2009;49(12):102–5.

    Google Scholar 

  37. Zhou J, Li B. Cost-effectiveness analysis of endoscope and omprazole in the treatment of acute hemorrhage of upper digestive tract. Lingnan J Emerg Med. 2013;18(6):453–6.

    Google Scholar 

  38. Xingbao C, Eggington S, Caiyun W, Min ZHU. Cost-effectiveness study of rivaroxaban for the prevention of venous thromboembolism in patients under going total knee replacement. China Pharm. 2011;22(30):2787–90.

    Google Scholar 

  39. Hogg K, Kimpton M, Carrier M, Coyle D, Forgie M, Wells P. Estimating quality of life in acute venous thrombosis. JAMA Intern Med. 2013;173(12):1067–72.

    Article  PubMed  Google Scholar 

  40. Rasanen P, Paavolainen P, Sintonen H, Koivisto AM, Blom M, Ryynanen OP, et al. Effectiveness of hip or knee replacement surgery in terms of quality-adjusted life years and costs. Acta Orthop. 2007;78(1):108–15.

    Article  PubMed  Google Scholar 

  41. Garin MC, Clark L, Chumney EC, Simpson KN, Highland KB. Cost-utility of treatments for pulmonary arterial hypertension: a Markov state-transition decision analysis model. Clin Drug Investig. 2009;29(10):635–46.

    Article  CAS  PubMed  Google Scholar 

  42. Bo H, Fu AZ. Predicting utility for joint health states: a general framework and a new nonparametric estimator. Med Decis Mak. 2010;30(5):E29–39.

  43. Wang Y, Zheng Y, Cai S, Fang L, Ni P. Efficacy and economics analysis of two anticoagulant schemes in the treatment of inpatients with pulmonary embolism. Chin J Drug Appl Monit. 2010;7(4):200–4.

    Google Scholar 

  44. Cao S. Pharmacoeconomic analysis of four strategies for treating deep vein thrombosis. J Huaihai Med. 2009;27(4):355–6.

    Google Scholar 

  45. Shen J, Sun Y, Liu H, Yao T, Bu J, Shen L, et al. Study on the cost-effect of combined therapy for patients with pulmonary arterial hypertension. J Intern Med Concepts Pract. 2008;3(6):416–9.

    Google Scholar 

  46. Craig BA, Black MA. Incremental cost-effectiveness ratio and incremental net-health benefit: two sides of the same coin. Expert Rev Pharmacoecon Outcomes Res. 2001;1(1):37–46.

    Article  CAS  PubMed  Google Scholar 

  47. Ryttberg L, Diamantopoulos A, Forster F, Lees M, Fraschke A, Bjorholt 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 

  48. Gomez-Outes A, Avendano-Sola C, Terleira-Fernandez AI, Vargas-Castrillon E. Pharmacoeconomic evaluation of dabigatran, rivaroxaban and apixaban versus enoxaparin for the prevention of venous thromboembolism after total hip or knee replacement in Spain. Pharmacoeconomics. 2014;32(9):919–36.

    Article  PubMed  Google Scholar 

  49. 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 

  50. Lewczuk J, Piszko P, Jagas J, Porada A, Wojciak S, Sobkowicz B, et al. Prognostic factors in medically treated patients with chronic pulmonary embolism. Chest. 2001;119(3):818–23.

    Article  CAS  PubMed  Google Scholar 

  51. Urushibara T, Tanabe N, Suda R, Kato F, Kasai H, Takeuchi T, et al. Effects of surgical and medical treatment on quality of life for patients with chronic thromboembolic pulmonary hypertension. Circ J. 2015;79(12):2696–702.

    Article  PubMed  Google Scholar 

  52. Schweikert B, Pittrow D, Vizza CD, Pepke-Zaba J, Hoeper MM, Gabriel A, et al. Demographics, clinical characteristics, health resource utilization and cost of chronic thromboembolic pulmonary hypertension patients: retrospective results from six European countries. BMC Health Serv Res. 2014;14:246.

    Article  PubMed  PubMed Central  Google Scholar 

  53. Eriksson BI, Borris LC, Friedman RJ, Haas S, Huisman MV, Kakkar AK, et al. Rivaroxaban versus enoxaparin for thromboprophylaxis after hip arthroplasty. N Engl J Med. 2008;358(26):2765–75.

    Article  CAS  PubMed  Google Scholar 

  54. 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 U.S. payer’s perspective. Pharmacoeconomics. 2012;30(2):87–101.

    Article  PubMed  Google Scholar 

Download references

Acknowledgments

The authors would like to thank Seng Chuen and Xingzhi Wang from IMS Health Asia Pacific for reviewing and editing the manuscript. We would like to thank the two anonymous reviewers and the editor for their very useful comments and suggestions, which helped us improve the quality of our paper.

Author information

Authors and Affiliations

  1. Department of Orthopedics, Shanghai Jiao Tong University Affiliated Sixth People’s Hospital, Shanghai, China

    Xiaoyu Yan

  2. Department of Respiratory Medicine, Shanghai Jiao Tong University Affiliated Sixth People’s Hospital, Shanghai, China

    Xiaohua Gu

  3. Department of Cardiology, Renji Hospital, School of Medicine, Shanghai Jiaotong University, Shanghai, China

    Lei Zhou

  4. Medical Decision and Economic Group, Department of Pharmacy, Renji Hospital, School of Medicine, Shanghai Jiaotong University, Pujian Road 160, Shanghai, 201112, China

    Houweng Lin & Bin Wu

Authors
  1. Xiaoyu Yan
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Xiaohua Gu
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Lei Zhou
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Houweng Lin
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Bin Wu
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Bin Wu.

Ethics declarations

Funding

This study was funded by Sanofi China. However, the study sponsor had no influence on the study design, data collection, or writing of the manuscript.

Conflict of interest statement

Dr. Wu has received a consulting fee from Sanofi China. None of the remaining authors has any personal or financial conflicts of interest.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Yan, X., Gu, X., Zhou, L. et al. Cost Effectiveness of Apixaban and Enoxaparin for the Prevention of Venous Thromboembolism After Total Knee Replacement in China. Clin Drug Investig 36, 1001–1010 (2016). https://doi.org/10.1007/s40261-016-0444-5

Download citation

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s40261-016-0444-5

Keywords

Search

Navigation