A PROBABILISTIC COST-EFFECTIVENESS ANALYSIS OF ENOXAPARIN VERSUS UNFRACTIONATED HEPARIN FOR THE PR OPHYLAXIS OF DEEP- VEIN THROMBOSIS FOLLOWING MAJOR TRAUMA

Main Article Content

Larry D Lynd
Ron Goeree
Mark A Crowther
Bernie J O’Brien

Keywords

Enoxaparin, heparin, thromboembolism, trauma

Abstract

Background


In the absence of major contraindications, treatment guidelines recommend that, following a major traumatic event, all patients receive low molecular weight heparin (e.g. enoxaparin) as thromboprophylaxis for the prevention of deep vein thrombosis (DVT).


 Objective


To estimate the incremental cost-effectiveness of enoxaparin versus low dose unfractionated heparin (UH) for the prophylaxis of DVT following major trauma.


 Methods


Using probabilistic decision-analytic modeling, we estimated the incremental cost-effectiveness of enoxaparin versus unfractionated heparin for the prophylaxis of DVT following moderate to severe trauma (injury severity score ?9) over a life-time time horizon from the perspective of the health care payer. Cost effectiveness was calculated based on both the incremental cost (DC) per DVT averted and the DC per life year gained (LYG).


 Results


The incremental cost of enoxaparin relative to UH was C$90, and the incremental effectiveness was 0.085 DVTs averted and -0.13 LYG. This resulted in an incremental cost-effectiveness ratio of C$1,059 per DVT averted, and the conclusion that UH is the dominant strategy in terms of LYG. In addition to the probabilistic analysis, one-way and two-way sensitivity analysis revealed that the model was most sensitive to variation in the discount rate (3% - 7%), but that UH remained the dominant strategy in terms of life years independent of the parameter estimates.


 Conclusions


Although enoxaparin appears to be a cost-effective alternative when considering the intermediate endpoint of DVTs averted, it may be dominated by UH in terms of LYG due to the higher incidence of major bleeds in patients receiving enoxaparin versus UH

Abstract 150 | PDF Downloads 77

References

1. Geerts WH, Code KI, Jay RM, Chen E, Szalai JP. A prospective study of venous thromboembolism after major trauma. N Engl J Med 1994;331(24):1601-6.
2. Kelsey LJ,Fry DM, VanderKolk WE. Thrombosis risk in the trauma patient. Prevention and treatment. Hematol Oncol Clin North Am 2000;14(2):417-30.
3. O'Malley KF, Ross SE. Pulmonary embolism in major trauma patients. J Trauma 1990;30(6):748-50.
4. Cook D, McMullin J, Hodder R, et al. Prevention and diagnosis of venous thromboembolism in critically ill patients: a Canadian survey.Crit Care 2001;5(6):336-42.
5. Lensing AW, Prandoni P, Brandjes D, et al. Detection of deep-vein thrombosis by real- time B-mode ultrasonography. N Engl J Med 1989;320(6):342 -5.
6. Rose SC, Zwiebel WJ, Nelson BD, et al. Symptomatic lower extremity d eep venous thrombosis: accuracy, limitations, and role of color duplex flow imaging in diagnosis. Radiology 1990;175(3):639-44.
7. Tapson VF, Carroll BA, Davidson BL, et al. The diagnostic approach to acute venous thromboembolism. Clinical practice guideli ne. American Thoracic Society. Am J Respir Crit Care Med 1999;160(3):1043-66.
8. Levine M, Gent M, Hirsh J, et al. A comparison of low- molecular-weight heparin administered primarily at home with unfractionated heparin administered in the hospital for proximal deep- vein thrombosis. N Engl J Med 1996;334(11):677-81.
9. Hirsh J, Lee AY. How we diagnose and treat deep vein thrombosis. Blood 2002;99(9):3102-10.
10. Kuijera PMM, Prins MH, Buller HR. Low molecular weight heparins: treatment of venous thromboembolism. In: Sasahara AA, Loscalzo J, editors. New therapeutic agents in thrombosis and thrombolysis. New York: M. Dekker; 1997. p. xiv, 681.
11. Hull RD, Raskob GE, Pineo GF, et al. Subcutaneous low-molecular-weight heparin compared with continuous intravenous heparin in the treatment of proximal- vein thrombosis. N Engl J Med 1992;326(15):975-82.
12. Levine MN, Raskob G, Landefeld S, Kearon C. Hemorrhagic complications of anticoagulant treatment. Chest 2001;119(1 Suppl):108S-121S.
13. Gallus A, Jackaman J, Til lett J, Mills W, Wycherley A. Safety and efficacy of warfarin started early after submassive venous thrombosis or pulmonary embolism. Lancet 1986;2(8519):1293 -6.
14. Hull RD, Raskob GE, Rosenbloom D, et al. Heparin for 5 days as compared with 10 days in the initial treatment of proximal venous thrombosis. N Engl J Med 1990;322(18):1260- 4.
15. Prandoni P, Lensing AW, Buller HR, et al. Comparison of subcutaneous low-molecular- weight heparin with intravenous standard heparin in proximal deep-vein thrombosis. Lancet 1992;339(8791):441- 5.
16. 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.
17. Knudson MM, Collins JA, Goodman SB, McCrory DW. Thromboembolism following multiple trauma. J Trauma 1992;32(1):2- 11.
18. Knudson MM, Morabito D, Paiement GD, Shackleford S. Use of low molecular weight heparin in preventing thromboembolism in trauma patients. J Trauma 1996;41(3):446-59.
19. O'Brien BJ, Anderson DR, Goeree R. Cost-effectiveness of enoxaparin versus warfarin prophylaxis against deep-vein thrombosis after total hip replacement. CMAJ 1994;150(7):1083-90.
20. Dalen JE, Alpert JS. Natural history of pulmonary embolism. Prog Cardiovasc Dis 1975;17(4):259-70.
21. O'Brien JA, Caro JJ. Direct medical cost of managing deep vein thrombosis according to the occurrence of complications. Pharmacoeconomics
2002;20(9):603-15.
22. Doubilet P, Begg CB, Weinstein MC, Braun P, McNeil BJ. Probabilistic sensitivity analysis using Monte Carlo simulation. A practical approach. Med Decis Making 1985;5(2):157-77.
23. Critchfield GC, Willard KE, Connoelly DP. Probabilistic sensitivity analysis methods for general decision models. Computers Biomed Res 1986;19:254-65.
24. Lynd LD, O'Brien BJ. Advances in risk-benefit evaluation using probabilistic simulation methods: an application to the prophylaxis of deep vein thrombosis. J Clin Epidemiol 2004;57:795-803.
25. Geerts WH, Jay RM, Code KI, et al. A comparison of low-dose heparin with low- molecular- weight heparin as prophylaxis against venous thromboembolism after major trauma. N Engl J Med 1996;335(10):701- 7.
26. Statistics Canada. Life tables: Canada, provinces, territories, 1995-1997. Ottawa, ON: Health Canada - Statistics Division; 2002. Report No.: 84- 537-XIE.
27. Briggs AH, O'Brien BJ, Blackhouse G. Thinking outside the box: recent advances in the analysis and presentation of uncertainty in cost- effectiveness studies. Annu Rev Public Health 2002;23:377-401.
28. Shorr AF, Ramage AS. Enoxaparin for thromboprophylaxis after major trauma: potential cost implications. Crit Care Med 2001;29(9):1659 -65.
29. Devlin JW, Petitta A, Shepard AD, Obeid FN.Cost -effectiveness of enoxaparin versus low- dose heparin for prophylaxis against venous thrombosis after major trauma. Pharmacotherapy 1998;18(6):1335 -42.
30. Sheldon TA. Problems of using modelling in the economic evaluation of health care. Health Econ 1996;5(1):1 -11.
31. Buxton MJ, Drummond MF, Van Hout BA, et al. Modelling in economic evaluation: an unavoidable fact of life. Health Econ 1997;6(3):217 -27.
32. Geerts WH, Pineo GF, Heit JA, et al. Prevention of venous thromboembolism: the Seventh ACCP Conference on Antithrombotic and Thrombolytic Therapy. Chest 2004;126(3 Suppl):338S-400S.
33. Weinstein MC, O'Brien B, Hornberger J, 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.
34. Kearon C. Noninvasive diagnosis of deep vein thrombosis in postoperative patients. Semin Thromb Hemost 2001;27(1):3-8.
35. Stein PD, Henry JW. Prevalence of acute pulmonary embolism in central and subsegme ntal pulmonary arteries and relation to probability interpretation of ventilation/perfusion lung scans. Chest 1997;111(5):1246-8.
36. Botteman MF, Caprini J, Stephens JM, 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.
37. Schwarcz TH, Quick RC, Minion DJ, Kearney PA, Kwolek CJ, Endean ED. Enoxaparin treatment in high -risk trauma patients limits the utility of surveillance venous duplex scanning. J Vasc Surg 2001;34(3):447 -52.
38. Legere BM, Dweik RA, Arroliga AC. Venous thromboembolism in the intensive care unit. Clin Chest Med 1999;20(2):367- 84.

Most read articles by the same author(s)