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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

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Abstract

Background: It has been estimated that major orthopaedic surgery has the highest risk of venous thromboembolism (deep vein thrombosis and pulmonary embolism) when compared with other surgery. Two new orally active anticoagulants have recently become licensed in Ireland for the primary prevention of venous thromboembolism in adult patients undergoing elective total hip replacement (THR) or total knee replacement (TKR). Rivaroxaban (Xarelto®) is a direct factor Xa inhibitor and dabigatran etexilate (Pradaxa®) is a prodrug of the active compound dabigatran, which inhibits thrombin.

Objective: To evaluate the cost effectiveness of rivaroxaban and dabigatran etexilate compared with enoxaparin sodium for the prophylaxis of venous thromboembolism in patients undergoing elective THR and TKR in the Irish healthcare setting.

Methods: The evaluation was conducted from the Irish health-payer perspective. A static decision-tree model was developed with a 180-day post-surgery time horizon. Separate models for the disease states THR and TKR were run to accommodate the different venous thromboembolism risks associated with each procedure. Outcome measures were QALYs and life-years gained (LYG). Costs were valued in ®, year 2008 values.

One-way sensitivity analysis of all probabilities in the model was performed. A probabilistic sensitivity analysis using second-order Monte Carlo simulation was performed to determine the probability of cost effectiveness at a €45 000 per QALY threshold.

Results: In the THR base-case model, rivaroxaban dominated both dabigatran etexilate and enoxaparin sodium. The incremental cost-effectiveness ratios for dabigatran etexilate relative to enoxaparin were €23 934 per LYG and €17 835 per QALY. In the TKR base-case model, rivaroxaban dominated both dabigatran etexilate and enoxaparin sodium. Dabigatran etexilate also dominated enoxaparin sodium.

In the one-way sensitivity analysis, the THR model was robust to all but four probability variations; the TKR model was robust to all variations.

At a cost-effectiveness threshold of €45 000 per QALY, the probability that rivaroxaban was the most cost-effective strategy after THR was 39%, followed by dabigatran etexilate at 32% and enoxaparin sodium at 29%. The probability that rivaroxaban was the most cost-effective strategy after TKR was 46%, followed by dabigatran etexilate at 30% and enoxaparin sodium at 24%.

Conclusion: Base-case analysis indicates that when both rivaroxaban and dabigatran etexilate are compared with enoxaparin sodium, rivaroxaban is the less costly and more effective option after THR and TKR. Probabilistic sensitivity analysis indicates that rivaroxaban is the most cost-effective strategy at a cost-effectiveness threshold of €45 000 per QALY; however, there is uncertainty regarding this strategy being more cost effective than dabigatran etexilate when both are compared with enoxaparin sodium.

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References

  1. Kearon C. Diagnosis of pulmonary embolism. CMAJ 2003; 168 (2): 183–94

    PubMed  Google Scholar 

  2. Geerts WH, Pineo GF, Heit JA. Prevention of venous thromboembolism: the Seventh ACCP Consensus Conference on Antithrombotic and Thrombolytic Therapy. Chest 2004; 126 (3 Suppl.): 338s-400s

    Article  Google Scholar 

  3. Heit J, Silverstein M, Mohr D, et al. Predictors of survival after deep vein thrombosis and pulmonary embolism: a population-based cohort study. Arch Intern Med 1999; 159: 445–53

    Article  PubMed  CAS  Google Scholar 

  4. Casemix. Ready reckoner of acute hospital inpatient activity and costs (summarised by DRG) relating to 2005 costs and activity (part 3). Dublin: Health Service Executive, 2007

    Google Scholar 

  5. Consumer Price Index for Health [online]. Available from URL: http://www.cso.ie/statistics/consumpriceindex.htm [Accessed 2008 Nov 1]

  6. National Institute for Health and Clinical Excellence. Venous thromboembolism: reducing the risk of venous thromboembolism (deep vein thrombosis and pulmonary embolism) in inpatients undergoing surgery. NICE clinical guideline 46. London: NICE, 2007 Apr [online]. Available from URL: http://www.nice.org.uk. [Accessed 2008 Aug 1]

  7. White R, Romano P, Zhou H. Incidence and time course of thromboembolic outcomes following total hip or knee arthroplasty. Arch Intern Med 1998; 158: 1525–31

    Article  PubMed  CAS  Google Scholar 

  8. Kearon C. Noninvasive diagnosis of deep vein thrombosis in postoperative patients. Semin Thromb Hemost 2001; 27: 3–8

    Article  PubMed  CAS  Google Scholar 

  9. Health Research and Information Division (HRID), The Economic and Social Research Institute (ESRI). Activity in acute public hospitals in Ireland, 2006 annual report. [online]. Available from URL: http://www.esri.ie/health_information/latest_hipe_nprs_reports/2006/HIPE_2006.pdf [Accessed 2008 Dec 1]

  10. Geerts W, Bergqvist D, Pineo G, et al. Prevention of venous thromboembolism: American College Of Chest Physicians evidence-based clinical practice guidelines. 8th ed. Chest 2008; 133 (6 Suppl.): 381s-453s

    Article  Google Scholar 

  11. Cohen A, Tapson V, Bergmann J. Venous thromboembolism risk and prophylaxis in the acute hospital care setting (ENDORSE study): a multinational cross-sectional study. Lancet 2008; 371: 387–94

    Article  PubMed  Google Scholar 

  12. Bayer Limited. Xarelto. IPHA Medicines Compendium, 2008 Oct 9 [online]. Available from URL: http://www.medicines.ie [Accessed 2008 Aug 12]

  13. Boehringer Ingelheim LTD. Pradaxa 110mg hard capsules. IPHA Medicines Compendium, 2008 Oct 30 [online]. Available from URL: http://www.medicines.ie [Accessed 2008 Aug 12]

  14. Kakkar A, Brenner B, Dahl O, 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. The RECORD 2 Investigators. Lancet 2008; 372 (9632): 31–9

    Article  PubMed  CAS  Google Scholar 

  15. Lassen M, Ageno W, Boris L, et al. Rivaroxaban versus enoxaparin for thromboprophylaxis after total knee arthroplasty. The RECORD 3 Investigators. N Engl J Med 2008; 358: 2776–86

    Article  PubMed  CAS  Google Scholar 

  16. Eriksson B, Dahl O, Rosencher N, et al. Dabigatran etexilate versus enoxaparin for the prevention of venous thromboembolism after total hip replacement: a randomised, double blind, non-inferiority trial. The RE-NOVATE Study Group. Lancet 2007; 370: 949–56

    Article  PubMed  CAS  Google Scholar 

  17. Eriksson B, Dahl O, Rosencher N, et al. Oral dabigatran etexilate vs subcutaneous enoxaparin for the prevention of venous thromboembolism after total knee replacement: the RE-MODEL randomised trial. J Thromb Haemost 2007; 5 (11): 2178–85

    Article  PubMed  CAS  Google Scholar 

  18. Baglin T, Keeling DM, Watson D. Guidelines on oral anticoagulation (warfarin). 3rd ed. (2005 update). British Society for Haematology 2005; 132: 277–85

    Article  Google Scholar 

  19. Buller H, Agnelli G, Hull R, et al. Antithrombotic therapy for venous thromboembolic disease. The Seventh ACCP Conference on Antithrombotic and Thrombolytic Therapy. Chest 2004; 126: 401S-28S

    Article  Google Scholar 

  20. Prandoni P, Villata S. The clinical course of deep vein thrombosis: prospective long term follow up of 528 symptomatic patients. Haematologica 1997; 82: 423–8

    PubMed  CAS  Google Scholar 

  21. Barry M, Tilson T. Recent developments in pricing and reimbursement of medicines in Ireland. Pharmacoeconomics Outcomes Res 2007; 7 (6): 605–11

    Article  Google Scholar 

  22. Nerurkar J, Wade W, Martin C. 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 

  23. Prescriber’s Guide. Dublin: St James’s Hospital, 2007

  24. Oster G, Tuden R, Colditz GA. A cost-effectiveness analysis of prophylaxis against deep-vein thrombosis in major orthopaedic surgery. JAMA 1987; 257: 203–8

    Article  PubMed  CAS  Google Scholar 

  25. Menzin J, Colditz G, Regan M, et al. Cost effectiveness of enoxaparin versus low dose warfarin in the prevention of deep-vein thrombosis after total hip replacment surgery. Arch Intern Med 1995; 155: 757–64

    Article  PubMed  CAS  Google Scholar 

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

    Article  CAS  Google Scholar 

  27. Douketis J, Kearon C, Bates S. Risk of fatal pulmonary embolism in patients with treated venous thromboembolism. JAMA 1998; 279 (6): 458–62

    Article  PubMed  CAS  Google Scholar 

  28. Stein P, Andjerald W, Henry M. Prevalence of acute pulmonary embolism among patients in a general hospital and at autopsy. Chest 1995; 108: 978–81

    Article  PubMed  CAS  Google Scholar 

  29. Lagerstedt C, Olsson C, Fagher BO. Need for long term anticoagulant therapy in symptomatic calf vein thrombosis. Lancet 1985; 2: 515–8

    Article  PubMed  CAS  Google Scholar 

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

    PubMed  CAS  Google Scholar 

  31. Cykert S, Phifer N, Hansen C. Tamoxifen for breast cancer prevention: a framework for clinical decisions. Obstet Gynecol 2004; 104 (3): 433–42

    Article  PubMed  CAS  Google Scholar 

  32. Lenert L, Soetikno R. Automated computer interviews to elicit utilities: potential application in the treatment of deep vein thrombosis. JAMA 1997; 4 (1): 49–56

    CAS  Google Scholar 

  33. Fryback D, Lawrence W. Dollars may not buy as many QALYs as we think: a problem with defining quality of life adjustments. Med Decis Making 1997; 17: 276–84

    Article  PubMed  CAS  Google Scholar 

  34. Monthly index of medical specialities (MIMS). Ireland. Dublin: Medical Publications (Ireland), 2008

  35. Drummond M, Jefferson T. Guidelines for authors and peer reviewers of economic submissions to the BMJ. BMJ 1996; 313: 275–83

    Article  PubMed  CAS  Google Scholar 

  36. Briggs A. Probabilistic analysis of cost-effectiveness models: stastistical representation of parameter uncertainty. Value Heath 2005; 8 (1): 1–2

    Article  Google Scholar 

  37. Gelman A, Carlin J, Stern H, et al. Bayesian data analysis. London: Chapman & Hall, 1995

    Google Scholar 

  38. Briggs A, Ades A, Price M. Probabilistic sensitivity analysis for decision trees with multiple branches: use of the Dirichlet distribution in a Bayesian framework. Med Decis Making 2003; 23: 341–50

    Article  PubMed  Google Scholar 

  39. O’Hagan A, Luce B. A primer on Bayesian statistics in health economics and outcomes research. Pennsylvania (PA): MEDTAP International, Inc., University of Pennsylvania, 2003

    Google Scholar 

  40. Botteman M, Caprini J, Stephens J, et al. Results of an economic model to access 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

    Article  PubMed  CAS  Google Scholar 

  41. Wolowacz S, Roskell N, Maciver F, 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 

  42. Haentjens P, De Groote K, Annemans L. Prolonged enoxaparin therapy to prevent venous thromboembolism after primary hip or knee replacement: a cost-utility analysis. Arch Orthop Trauma Surg 2004; 124: 507–17

    Article  PubMed  Google Scholar 

  43. Gordois A, Posnett J, Borris L, et al. The cost-effectiveness of fondaparinux compared with enoxaparin as prophylaxis against thromboembolism following major orthopaedic surgery. J Thromb Haemost 2003; 1: 2167–74

    Article  PubMed  CAS  Google Scholar 

  44. Sculpher M, Claxton K. Establishing the cost-effectiveness of new pharmaceuticals under conditions of uncertainty: when is there sufficient evidence? Value Health 2005; 8 (4): 433–66

    Article  PubMed  Google Scholar 

  45. Weinstein M, O’Brien B, Hornberger M, et al. Principles of good practice for decision analytic modeling in health-care evaluation: report of the ISPOR task force on good research practices-modeling studies. Value Health 2003; 6 (1): 9–17

    Article  PubMed  Google Scholar 

  46. Barton G, Briggs A, Fenwick E. Optimal cost-effectiveness decisions: the role of the cost-effectiveness acceptability curve (CEAC), the cost-effectiveness acceptability frontier (CEAF), and the expected value of perfection information (EVPI). Value Heath 2008; 11 (5): 886–97

    Article  Google Scholar 

  47. Claxton K. Exploring uncertainty in cost-effectiveness analysis. Pharmacoeconomics 2008; 26 (9): 781–98

    Article  PubMed  Google Scholar 

  48. Sutton A, Ades AE, Cooper N, et al. Use of indirect and mixed treatment comparisons for technology assessment. Pharmacoeconomics 2008; 26 (9): 753–67

    Article  PubMed  Google Scholar 

  49. Song F, Altman DG, Glenny AM, et al. Validity of indirect comparison for estimating efficacy of competing interventions: empirical evidence from published meta-analyses. BMJ 2003; 326 (7387): 472–5

    Article  PubMed  Google Scholar 

  50. Sullivan S, Kalm S, Davidson B, et al. Measuring the outcome and pharmacoeconomic consequences of venous thromboembolism prophylaxis in major orthopaedic surgery. Pharmacoeconomics 2003; 21 (7): 477–96

    Article  PubMed  Google Scholar 

  51. Ramzi D, Leeper K. DVT and pulmonary embolism: part 1. Diagnosis. Am Fam Physician 2004; 69 (12): 2841–8

    Google Scholar 

  52. White R. Low-molecular-weight-heparins: are they all the same? Br J Haematol 2003; 121: 12–20

    Article  PubMed  CAS  Google Scholar 

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No sources of funding were used to assist in the preparation of this study. The authors have no conflicts of interest that are directly relevant to the content of this study.

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Correspondence to Laura McCullagh.

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McCullagh, L., Tilson, L., Walsh, C. et al. 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 27, 829–846 (2009). https://doi.org/10.2165/11313800-000000000-00000

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