Skip to main content
Top
Published in: PharmacoEconomics 5/2017

01-05-2017 | Systematic Review

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

Authors: James Brockbank, Sorrel Wolowacz

Published in: PharmacoEconomics | Issue 5/2017

Login to get access

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.
Appendix
Available only for authorised users
Literature
1.
go back to reference 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.CrossRefPubMed 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.CrossRefPubMed
2.
go back to reference 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.CrossRefPubMedPubMedCentral 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.CrossRefPubMedPubMedCentral
4.
go back to reference 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.CrossRefPubMed 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.CrossRefPubMed
5.
go back to reference 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.CrossRefPubMedPubMedCentral 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.CrossRefPubMedPubMedCentral
6.
go back to reference 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.CrossRefPubMed 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.CrossRefPubMed
7.
go back to reference 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.PubMed 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.PubMed
8.
go back to reference 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.CrossRefPubMedPubMedCentral 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.CrossRefPubMedPubMedCentral
9.
go back to reference 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.CrossRefPubMedPubMedCentral 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.CrossRefPubMedPubMedCentral
10.
go back to reference 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.CrossRefPubMed 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.CrossRefPubMed
11.
go back to reference 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.CrossRefPubMed 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.CrossRefPubMed
12.
go back to reference 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.CrossRefPubMed 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.CrossRefPubMed
13.
go back to reference 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.CrossRefPubMed 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.CrossRefPubMed
14.
go back to reference 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.CrossRefPubMed 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.CrossRefPubMed
15.
go back to reference 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 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
16.
go back to reference 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.CrossRefPubMed 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.CrossRefPubMed
17.
go back to reference 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.CrossRefPubMed 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.CrossRefPubMed
18.
go back to reference 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.CrossRefPubMed 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.CrossRefPubMed
19.
go back to reference Migliaccio-Walle K, Rublee D, Simon TA. Anticoagulation prophylaxis in orthopedic surgery: an efficiency frontier approach. Postgrad Med. 2012;124(1):41–9.CrossRefPubMed Migliaccio-Walle K, Rublee D, Simon TA. Anticoagulation prophylaxis in orthopedic surgery: an efficiency frontier approach. Postgrad Med. 2012;124(1):41–9.CrossRefPubMed
20.
go back to reference 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. 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.
21.
go back to reference 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.CrossRefPubMed 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.CrossRefPubMed
23.
go back to reference 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.CrossRefPubMed 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.CrossRefPubMed
24.
go back to reference 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.CrossRefPubMed 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.CrossRefPubMed
25.
go back to reference 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.CrossRefPubMedPubMedCentral 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.CrossRefPubMedPubMedCentral
26.
go back to reference 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.CrossRefPubMed 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.CrossRefPubMed
27.
go back to reference 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.CrossRefPubMed 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.CrossRefPubMed
28.
go back to reference 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.CrossRefPubMed 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.CrossRefPubMed
29.
go back to reference 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.CrossRefPubMed 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.CrossRefPubMed
30.
go back to reference 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.CrossRefPubMed 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.CrossRefPubMed
31.
go back to reference 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.CrossRefPubMed 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.CrossRefPubMed
32.
go back to reference 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.CrossRefPubMed 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.CrossRefPubMed
33.
go back to reference 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.CrossRefPubMed 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.CrossRefPubMed
34.
go back to reference 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.CrossRefPubMed 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.CrossRefPubMed
35.
go back to reference 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.CrossRefPubMed 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.CrossRefPubMed
Metadata
Title
Economic Evaluations of New Oral Anticoagulants for the Prevention of Venous Thromboembolism After Total Hip or Knee Replacement: A Systematic Review
Authors
James Brockbank
Sorrel Wolowacz
Publication date
01-05-2017
Publisher
Springer International Publishing
Published in
PharmacoEconomics / Issue 5/2017
Print ISSN: 1170-7690
Electronic ISSN: 1179-2027
DOI
https://doi.org/10.1007/s40273-017-0486-4

Other articles of this Issue 5/2017

PharmacoEconomics 5/2017 Go to the issue