The European Journal of Health Economics

, Volume 8, Issue 4, pp 313–323

Cost-effectiveness of extended prophylaxis with fondaparinux compared with low molecular weight heparin against venous thromboembolism in patients undergoing hip fracture surgery

Original paper


A model was developed to estimate costs and clinical effectiveness of fondaparinux compared with enoxaparin after hip fracture surgery in Sweden. Outcomes and costs of venous thromboembolism (VTE)-related care from a health care perspective were incorporated, with symptomatic deep-vein thrombosis and pulmonary embolism, recurrent VTE, post-thrombotic syndrome, major haemorrhage and all-cause death being included. Event probabilities were derived from fondaparinux clinical trial data and published data. VTE-related resource use and associated costs as well as costs of prophylaxis were based on local Swedish data. Extended prophylaxis with fondaparinux could avoid an additional 28 symptomatic VTE per 1,000 patients compared with extended prophylaxis with enoxaparin in hip fracture surgery patients. Although the prophylaxis costs were higher in the fondaparinux group, these were offset by the lower costs associated with treating fewer VTE, which thus indicates that extended fondaparinux prophylaxis is the dominant alternative when compared with enoxaparin in hip fracture surgery.


Venous thrombosis Surgery Deep vein thrombosis Pulmonary embolism Cost-effectiveness 

JEL Classification



  1. 1.
    Blodpropp-förebyggande, diagnostik o behandling av venös tromboembolism (in Swedish): The Swedish Council on Technology Assessment in Health Care (SBU), Linköping (2002)Google Scholar
  2. 2.
    Saunders, M.E., Grant, R.E.: Cost effectiveness of low-molecular weight heparin versus warfarin following hip replacement surgery. J. Natl. Med. Assoc. 90(11), 677–680 (1998)Google Scholar
  3. 3.
    Menzin, J., Colditz, G.A., Regan, M.M., Richner, R.E., 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. 155(7), 757–764 (1995)CrossRefGoogle Scholar
  4. 4.
    Lundkvist, J., Bergqvist, D., Jönsson, B.: Cost effectiveness of fondaparinux compared to enoxaparin as venous thromboembolism prophylaxis in Sweden. Eur. J. Health Econ. 4(4), 254–262 (2003)CrossRefGoogle Scholar
  5. 5.
    Balen, R.M., Marra, C.A., Zed, P.J., Cohen, M., Frighetto, L.: Cost-effectiveness analysis of enoxaparin versus unfractionated heparin for acute coronary syndromes. A Canadian hospital perspective. Pharmacoeconomics 16(5 Pt 2), 533–542 (1999)CrossRefGoogle Scholar
  6. 6.
    Bergqvist, D.: Enoxaparin: a pharmacoeconomic review of its use in the prevention and treatment of venous thromboembolism and in acute coronary syndromes. Pharmacoeconomics 20(4), 225–243 (2002)CrossRefGoogle Scholar
  7. 7.
    Geerts, W.H., Heit, J.A., Clagett, G.P., Pineo, G.F., Colwell, C.W., et al.: Prevention of venous thromboembolism. Chest 119(1 Suppl), 132S–175S (2001)CrossRefGoogle Scholar
  8. 8.
    Data on file, Sanofi-Synthelabo (2003)Google Scholar
  9. 9.
    Eikelboom, J.W., Quinlan, D.J., Douketis, J.D.: Extended-duration prophylaxis against venous thromboembolism after total hip or knee replacement: a meta-analysis of the randomised trials. Lancet 358(9275), 9–15 (2001)CrossRefGoogle Scholar
  10. 10.
    Bergqvist, D., Jonsson, B.: Cost-effectiveness of prolonged out-of-hospital prophylaxis with low-molecular-weight heparin following total hip replacement. Haemostasis 30 Suppl 2130–2135; discussion 128–129 (2000)Google Scholar
  11. 11.
    Hull, R.D., Pineo, G.F., Stein, P.D., Mah, A.F., MacIsaac, S.M., et al.: Extended out-of-hospital low-molecular-weight heparin prophylaxis against deep venous thrombosis in patients after elective hip arthroplasty: a systematic review. Ann. Intern. Med. 135(10), 858–869 (2001)Google Scholar
  12. 12.
    Davies, L., Richardson, G., Cohen, A.: Economic evaluation of enoxaparin as postdischarge prophylaxis for deep vein thrombosis (DVT) in elective hip surgery. Value Health 3(6), 397–406 (2000)CrossRefGoogle Scholar
  13. 13.
    Detournay, B., Planes, A., Vochelle, N., Fagnani, F.: Cost effectiveness of a low-molecular-weight heparin in prolonged prophylaxis against deep vein thrombosis after total hip replacement. Pharmacoeconomics 13(1 Pt 1), 81–89 (1998)CrossRefGoogle Scholar
  14. 14.
    Eriksson, B.I., Lassen, M.R.: Duration of prophylaxis against venous thromboembolism with fondaparinux after hip fracture surgery: a multicenter, randomized, placebo-controlled, double-blind study. Arch. Intern. Med. 163(11), 1337–42 (2003)CrossRefGoogle Scholar
  15. 15.
    Gordois, A.: The cost-effectiveness of fondaparinux compared with enoxaparin as prophylaxis against thromboembolism following major orthopedic surgery. J. Thromb. Haemost. 1(10), 2167–2174 (2003)CrossRefGoogle Scholar
  16. 16.
    Sullivan, S.: Cost-effectiveness of fondaparinux compared with enoxaparin as prophylaxi against venous thromboembolsim in patients undergoing major orthopedic surgery. Blood 100(11), 871 (2002)Google Scholar
  17. 17.
    Lassen, M.R., Borris, L.C., Anderson, B.S., Jensen, H.P., Skejo Bro, H.P., et al.: Efficacy and safety of prolonged thromboprophylaxis with a low molecular weight heparin (dalteparin) after total hip arthroplasty–the Danish Prolonged Prophylaxis (DaPP) Study. Thromb. Res. 89(6), 281–287 (1998)CrossRefGoogle Scholar
  18. 18.
    Turpie, A.G., Bauer, K.A., Eriksson, B.I., Lassen, M.R.: Postoperative fondaparinux versus postoperative enoxaparin for prevention of venous thromboembolism after elective hip-replacement surgery: a randomised double-blind trial. Lancet 359(9319), 1721–1726 (2002)CrossRefGoogle Scholar
  19. 19.
    Eriksson, B.I., Bauer, K.A., Lassen, M.R., Turpie, A.G.: Fondaparinux compared with enoxaparin for the prevention of venous thromboembolism after hip-fracture surgery. N. Engl. J. Med. 345(18), 1298–1304 (2001)CrossRefGoogle Scholar
  20. 20.
    White, R.H., Romano, P.S., Zhou, H., Rodrigo, J., Bargar, W.: Incidence and time course of thromboembolic outcomes following total hip or knee arthroplasty. Arch. Intern. Med. 158(14), 1525–1531 (1998)CrossRefGoogle Scholar
  21. 21.
    Devlin, J.W., Petitta, A., Shepard, A.D., Obeid, F.N.: Cost-effectiveness of enoxaparin versus low-dose heparin for prophylaxis against venous thrombosis after major trauma. Pharmacotherapy 18(6), 1335–1342 (1998)Google Scholar
  22. 22.
    Drummond, M., Aristides, M., Davies, L., Forbes, C.: Economic evaluation of standard heparin and enoxaparin for prophylaxis against deep vein thrombosis in elective hip surgery. Br. J. Surg. 81(12), 1742–1746 (1994)CrossRefGoogle Scholar
  23. 23.
    Hillson, S.D., Rich, E.C.: Two strategies for prophylaxis of fatal postoperative pulmonary embolism. Cost-effectiveness analysis. Int. J. Technol. Assess Health Care 6(3), 470–479 (1990)CrossRefGoogle Scholar
  24. 24.
    Hawkins, D.W., Langley, P.C., Krueger, K.P.: Pharmacoeconomic model of enoxaparin versus heparin for prevention of deep vein thrombosis after total hip replacement. Am. J. Health Syst. Pharm. 54(10), 1185–1190 (1997)Google Scholar
  25. 25.
    Levin, L.A., Horst, M., Bergqvist, D.: Economic evaluation of desirudin vs heparin in deep vein thrombosis prevention after hip replacement surgery. Pharmacoeconomics 13(1 Pt 2), 111–118 (1998)CrossRefGoogle Scholar
  26. 26.
    Levin, L.A., Bergqvist, D.: Cost effectiveness of desirudin compared with a low molecular weight heparin in the prevention of deep vein thrombosis after total hip replacement surgery. Pharmacoeconomics 19(5 Pt 2), 589–597 (2001)CrossRefGoogle Scholar
  27. 27.
    Lloyd, A: Economic evaluation of the use of enoxaparin for thomboprophylaxis in acutely ill medical patients. J. Drug Assess. 4145–159Google Scholar
  28. 28.
    Lloyd, A., Aitken, J.A., Hoffmeyer, U.K., Kelso, E.J., Wakerly, E.C., et al.: Economic evaluation of the use of nadroparin calcium in the prophylaxis of deep vein thrombosis and pulmonary embolism in surgical patients in Italy. Pharmacoeconomics 12(4), 475–485 (1997)Google Scholar
  29. 29.
    Nicolaides, A., Bosanquet, N.: Cost-effectiveness of desirudin in the prevention of the thromboemebolism complications of surgery. J. Drug Assess. 2353–2364 (1999)Google Scholar
  30. 30.
    O’Brien, B.J., Anderson, D.R., Goeree, R.: Cost-effectiveness of enoxaparin versus warfarin prophylaxis against deep-vein thrombosis after total hip replacement. Cmaj 150(7), 1083–1090 (1994)Google Scholar
  31. 31.
    Oster, G., Tuden, R.L., Colditz, G.A.: A cost-effectiveness analysis of prophylaxis against deep-vein thrombosis in major orthopedic surgery. JAMA 257(2), 203–8 (1987)CrossRefGoogle Scholar
  32. 32.
    Oster, G., Tuden, R.L., Colditz, G.A.: Prevention of venous thromboembolism after general surgery. Cost-effectiveness analysis of alternative approaches to prophylaxis. Am. J. Med. 82(5), 889–99 (1987)CrossRefGoogle Scholar
  33. 33.
    Pechevis, M.: Economic evaluation of enoxaparin vs. placebo for the prevention of venous thromboembolism in acutely III medical patients. Value Health 3(6), 389–396 (2000)CrossRefGoogle Scholar
  34. 34.
    Szucs, T.D., Schramm, W.: The cost-effectiveness of low-molecular-weight heparin vs unfractionated heparin in general and orthopaedic surgery: an analysis for the German healthcare system. Pharmacol. Res. 40(1), 83–89 (1999)CrossRefGoogle Scholar
  35. 35.
    Prandoni, P., Lensing, A.W., Cogo, A., Cuppini, S., Villalta, S., et al.: The long-term clinical course of acute deep venous thrombosis. Ann. Intern. Med. 125(1), 1–7 (1996)Google Scholar
  36. 36.
    Hull, R., Delmore, T., Carter, C., Hirsh, J., Genton, E., et al.: Adjusted subcutaneous heparin versus warfarin sodium in the long-term treatment of venous thrombosis. N. Engl. J. Med. 306(4), 189–194 (1982)CrossRefGoogle Scholar
  37. 37.
    Hull, R., Hirsh, J., Jay, R., Carter, C., England, C., et al.: Different intensities of oral anticoagulant therapy in the treatment of proximal-vein thrombosis. N. Engl. J. Med. 307(27), 1676–1681 (1982)CrossRefGoogle Scholar
  38. 38.
    Lagerstedt, C.I., Olsson, C.G., Fagher, B.O., Oqvist, B.W., Albrechtsson, U.: Need for long-term anticoagulant treatment in symptomatic calf-vein thrombosis. Lancet 2(8454), 515–518 (1985)CrossRefGoogle Scholar
  39. 39.
    Pini, M., Aiello, S., Manotti, C., Pattacini, C., Quintavalla, R., et al.: Low molecular weight heparin versus warfarin in the prevention of recurrences after deep vein thrombosis. Thromb. Haemost. 72(2), 191–197 (1994)Google Scholar
  40. 40.
    Schulman, S., Rhedin, A.S., Lindmarker, P., Carlsson, A., Larfars, G., et al.: A comparison of six weeks with six months of oral anticoagulant therapy after a first episode of venous thromboembolism. Duration of Anticoagulation Trial Study Group. N. Engl. J. Med. 332(25), 1661–1665 (1995)CrossRefGoogle Scholar
  41. 41.
    Das, S.K., Cohen, A.T., Edmondson, R.A., Melissari, E., Kakkar, V.V.: Low-molecular-weight heparin versus warfarin for prevention of recurrent venous thromboembolism: a randomized trial. World J. Surg. 20(5), 521–526; discussion 526–527 (1996)Google Scholar
  42. 42.
    Ginsberg, J.S., Turkstra, F., Buller, H.R., MacKinnon, B., Magier, D., et al.: Postthrombotic syndrome after hip or knee arthroplasty: a cross-sectional study. Arch. Intern. Med. 160(5), 669–672 (2000)CrossRefGoogle Scholar
  43. 43.
    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. Minerva Cardioangiol. 45(3), 57–66 (1997)Google Scholar
  44. 44.
    Life tables. Statistic Sweden, Stockholm (2003)Google Scholar
  45. 45.
    Johnell, O., Kanis, J.A., Oden, A., Sernbo, I., Redlund-Johnell, I., et al.: Mortality after osteoporotic fractures. Osteoporos. Int. 15(1), 38–42 (2004)CrossRefGoogle Scholar
  46. 46.
    Braithwaite, R.S., Col, N.F., Wong, J.B.: Estimating hip fracture morbidity, mortality and costs. J. Am. Geriatr. Soc. 51(3), 364–370 (2003)CrossRefGoogle Scholar
  47. 47.
    Kanis, J.A., Oden, A., Johnell, O., De Laet, C., Jonsson, B., et al.: The components of excess mortality after hip fracture. Bone 32(5), 468–473 (2003)CrossRefGoogle Scholar
  48. 48.
    Manning, W.G.: The logged dependent variable, heteroscedasticity, and the retransformation problem. J. Health Econ. 17(3), 283–295 (1998)CrossRefGoogle Scholar
  49. 49.
    Manning, W.G., Mullahy, J.: Estimating log models: to transform or not to transform? J. Health Econ. 20(4), 461–494 (2001)CrossRefGoogle Scholar
  50. 50.
    LINFO FASS Läkemedel i Sverige (Swedish drug prices). Läkemedelsinformation AB: Oslo (2003)Google Scholar
  51. 51.
    STIQS project-fifth report (Data on file, Sanofi Synthelabo) (2003)Google Scholar
  52. 52.
    Lapidus, L., Borretzen, J., Fahlen, M., Thomsen, H.G., Hasselblom, S., et al.: Home treatment of deep vein thrombosis. An out-patient treatment model with once-daily injection of low-molecular-weight heparin (tinzaparin) in 555 patients. Pathophysiol. Haemost. Thromb. 32(2), 59–66 (2002)CrossRefGoogle Scholar
  53. 53.
    Landstingsförbundet, Kostnad per intagen patient (Cost per admitted patient). Stockholm County Council (1999)Google Scholar
  54. 54.
    Dahl, O.E., Andreassen, G., Aspelin, T., Muller, C., Mathiesen, P., et al.: Prolonged thromboprophylaxis following hip replacement surgery—results of a double-blind, prospective, randomised, placebo-controlled study with dalteparin (Fragmin). Thromb. Haemost. 77(1), 26–31 (1997)Google Scholar
  55. 55.
    Manganelli, D., Pazzagli, M., Mazzantini, D., Punzi, G., Manca, M., et al.: Prolonged prophylaxis with unfractioned heparin is effective to reduce delayed deep vein thrombosis in total hip replacement. Respiration 65(5), 369–374 (1998)CrossRefGoogle Scholar
  56. 56.
    Heit, J.A., Elliott, C.G., Trowbridge, A.A., Morrey, B.F., Gent, M., et al.: Ardeparin sodium for extended out-of-hospital prophylaxis against venous thromboembolism after total hip or knee replacement. A randomized, double-blind, placebo-controlled trial. Ann. Intern. Med. 132(11), 853–861 (2000)Google Scholar
  57. 57.
    Leclerc, J.R., Gent, M., Hirsh, J., Geerts, W.H., Ginsberg, J.S.: The incidence of symptomatic venous thromboembolism after enoxaparin prophylaxis in lower extremity arthroplasty: a cohort study of 1,984 patients. Canadian Collaborative Group. Chest 114(2 Suppl Evidence), 115S–118S (1998)Google Scholar
  58. 58.
    Colwell, C.W. Jr., Collis, D.K., Paulson, R., McCutchen, J.W., Bigler, G.T., et al.: Comparison of enoxaparin and warfarin for the prevention of venous thromboembolic disease after total hip arthroplasty. Evaluation during hospitalization and three months after discharge. J. Bone Joint Surg. Am. 81(7), 932–40 (1999)Google Scholar
  59. 59.
    Pellegrini, V.D. Jr., Clement, D., Lush-Ehmann, C., Keller, G.S., Evarts, C.M.: The John Charnley Award. Natural history of thromboembolic disease after total hip arthroplasty. Clin Orthop (333), 27–40 (1996)Google Scholar
  60. 60.
    Hansson, P.O., Sorbo, J., Eriksson, H.: Recurrent venous thromboembolism after deep vein thrombosis: incidence and risk factors. Arch. Intern. Med. 160(6), 769–74 (2000)CrossRefGoogle Scholar

Copyright information

© Springer-Verlag 2007

Authors and Affiliations

  • Jonas Lundkvist
    • 1
    • 2
  • David Bergqvist
    • 3
  • Bengt Jönsson
    • 4
  1. 1.European Health EconomicsStockholmSweden
  2. 2.Medical Management CentreKarolinska InstitutetStockholmSweden
  3. 3.Department of Surgical ScienceAkademiska HospitalUppsalaSweden
  4. 4.Stockholm School of EconomicsStockholmSweden

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