PharmacoEconomics

, Volume 17, Issue 1, pp 1–12 | Cite as

Formulary Management of Low Molecular Weight Heparins

  • William E. Wade
  • Bradley C. Martin
  • Jeffrey A. Kotzan
  • William J. Spruill
  • Marie A. Chisoholm
  • Matthew Perri
Review Article

Abstract

Low molecular weight heparins (LMWHs) are increasingly being utilised as anticoagulants in healthcare settings. These agents offer several advantages over standard unfractionated heparin. Indications for LMWHs include deep vein thrombosis and pulmonary embolism prophylaxis, deep vein thrombosis treatment, use in coronary procedures associated with a high risk for bleeding, and in acute coronary syndromes.

Prior to being added to formularies, LMWHs should be evaluated for efficacy, safety and economic benefits over other anticoagulants. Institutions should be prepared to conduct their own economic assessments in the absence of readily available studies.

There is clear evidence that LMWHs are cost saving or are at least cost effective as thromboprophylactic agents in major orthopaedic surgery. The economic benefits of LMWHs in other surgical situations is less clear. Consistent evidence from several countries indicate that LMWHs are cost saving as anticoagulants for the initial treatment of DVT.

Further studies are needed to evaluate the efficacy, safety and economics of LMWHs in other conditions besides hip and knee arthroplasty and general surgery.

References

  1. 1.
    Ofosu FA, Barrowcliffe TW. Mechanisms of action of low molecular weight heparins and heparinoids. In: Hirsh J, editor. Antithrombotic therapy, Bailliere’s clinical hematology. Vol. 3. London: Bailliere Tindall, 1990: 505–29Google Scholar
  2. 2.
    Bara L, Billaud E, Gramond G, et al. Comparative pharmacokinetics of low molecular weight heparin (PK 10169) and unfractionated heparin after intravenous and subcutaneous administration. Thromb Res 1985; 39 (5): 631–6PubMedGoogle Scholar
  3. 3.
    Young E, Wells P, Holloway S, et al. Ex-vitro and in-vitro evidence that low molecular weight heparins exhibit less binding to plasma proteins than unfractionated heparin. Thromb Haemost 1994; 71 (3): 300–4PubMedGoogle Scholar
  4. 4.
    Handeland GF, Abildgaard U, Holm HA, et al. Dose adjusted heparin treatment of deep venous thrombosis: a comparison of unfractionated and low molecular weight heparin. Eur J Clin Pharmacol 1990; 39 (2): 107–12PubMedGoogle Scholar
  5. 5.
    Sobel M, McNeill PM, Carlson PL, et al. Heparin inhibition of von Wille brand factor-dependent platelet function in vitro and in in vivo. J Clin Invest 1991; 87 (5): 1787–93PubMedGoogle Scholar
  6. 6.
    Bradbrook ID, Magnani HN, Moelker HC, et al. ORG 10172: a low molecular weight heparinoid anticoagulant with a long half life in man. Br J Clin Pharmacol 1987; 23 (6): 667–75PubMedGoogle Scholar
  7. 7.
    Bratt G, Tornebohm E, Widlund L, et al. Low molecular weight heparin (KABI 2165, FRAGMIN): pharmacokinetics after intravenous and subcutaneous administration in human volunteers. Thromb Res 1986; 42 (5): 613–20PubMedGoogle Scholar
  8. 8.
    Frydman A, Bara L, Le Roux Y, et al. The antithrombotic activity and pharmacokinetics of enoxaparin, a low molecular weight heparin, in man given single subcutaneous doses of 20 up to 80mg. J Clin Pharmacol 1988; 28 (7): 606–18Google Scholar
  9. 9.
    Mätzsch T, Bergqvist D, Hedner U, et al. Effect of enzymatically depolymerized heparin as compared with conventional heparin in healthy volunteers. Thromb Haemost 1987; 57 (1): 97–101PubMedGoogle Scholar
  10. 10.
    Stiekema JC, Wijnand HP, Van Dinther TG, et al. Safety and pharmacokinetics of the low molecular weight heparinoid ORG 10172 administered to healthy volunteers. Br J Clin Pharmacol 1989; 27 (1): 39–48PubMedGoogle Scholar
  11. 11.
    Warkentin TE, Levine MN, Hirsh J, et al. Heparin-induced thrombocytopenia in patients treated with low-molecular weight heparin or unfractionated heparin. N Engl J Med 1995; 332 (20): 1330–5PubMedGoogle Scholar
  12. 12.
    Hirsh J, Warkentin TE, Raschke R, et al. Heparin and low-molecular-weight heparin: mechanisms of action, pharmacokinetics, dosing considerations, monitoring, efficacy, and safety. Chest 1998; 114 Suppl. 5: 489S-510SGoogle Scholar
  13. 13.
    Cade JF, Buchanan MR, Boneu B, et al. A comparison of the antithrombotic and hemorrhagic effects of low molecular weight heparin fractions: the influence of the method of preparation. Thromb Res 1984; 35 (3): 613–25PubMedGoogle Scholar
  14. 14.
    Carter CJ, Kelton JG, Hirsh J, et al. The relationship between the hemorrhagic and antithrombotic properties of low molecular weight heparins and heparin. Blood 1982; 59 (6): 1239–45PubMedGoogle Scholar
  15. 15.
    Esquivel CO, Bergqvist D, Bjorck C-G, et al. Comparison between commercial heparin, low- molecular weight heparin and pentosan polysulphate on haemostasis and platelets in vivo. Thromb Res 1982; 28 (3): 389–99PubMedGoogle Scholar
  16. 16.
    Ockelford PA, Carter CJ, Mitchell L, et al. Discordance between the anti-Xa activity and antithrombotic activity of an ultralow molecular weight heparin fraction. Thromb Res 1982; 28 (3): 401–9PubMedGoogle Scholar
  17. 17.
    Nurmohamed MT, ten Cate H, ten Cate JW. Low molecular weight heparin(oid)s: clinical investigations and practical recommendations. Drugs 1997; 53 (5): 736–51PubMedGoogle Scholar
  18. 18.
    Heaton D, Pearce M. Low molecular weight versus unfractionated heparin: a clinical and economic appraisal. Pharmacoeconomics 1995; 8 (8): 91–9PubMedGoogle Scholar
  19. 19.
    Chaffee BJ. Low-molecular-weight heparins for treatment of deep vein thrombosis. Am J Health Syst Pharm 1997; 54 (17): 1995–9PubMedGoogle Scholar
  20. 20.
    Nilsson PE, Bergqvist D, Benoni G, et al. The post-discharge prophylactic management of the orthopedic patient with low molecular- weight heparin: enoxaparin. Orthopedics 1997; 20: 22–5PubMedGoogle Scholar
  21. 21.
    Weitz JI. Low-molecular-weight heparins. N Engl J Med 1997; 337 (10): 688–98PubMedGoogle Scholar
  22. 22.
    Kakkar VV, Cohen AT, Edmonson RA, et al. Low molecular weight heparin versus standard heparin for prevention of venous thromboembolism after major abdominal surgery. Lancet 1993; 341 (8840): 259–65PubMedGoogle Scholar
  23. 23.
    Jorgensen LN, Wille-Jorgensen P, Hauch O. Prophylaxis of postoperative thromboembolism with low molecular weight heparins. Br J Surg 1993; 80 (6): 689–704PubMedGoogle Scholar
  24. 24.
    Leizorovicz A, Haugh MC, Chapuis F-R, et al. Low molecular weight heparin in the prevention of perioperative thrombosis. BMJ 1992; 305 (6859): 913–20PubMedGoogle Scholar
  25. 25.
    Nurmohamed MT, Verhaeghe R, Haas S, et al. A comparative trial of a low molecular weight heparin (enoxaparin) for the prophylaxis of postoperative deep vein thrombosis in general surgery. Am J Surg 1995; 169 (6): 567–71PubMedGoogle Scholar
  26. 26.
    Bergqvist D, Burmark US, Flordal PA, et al. Low molecular weight heparin started before surgery as prophylaxis against deep vein thrombosis: 2500 versus 5000 XaI units in 2070 patients. Br J Surg 1995; 82 (4): 496–501PubMedGoogle Scholar
  27. 27.
    Hartl P, Brucke P, Dienstl E, et al. Prophylaxis of thromboembolism in general surgery: comparison between standard heparin and fragmin. Thromb Res 1990; 57 (4): 577–84PubMedGoogle Scholar
  28. 28.
    Boneu B. An international multicenter study - clivarin (r) in the prevention of venous thromboembolism in patients undergoing general surgery: report of the International Clivarin (r) Assessment Group. Blood Coagul Fibrinolysis 1993; 4 Suppl. 1: S21–32Google Scholar
  29. 29.
    Ward B, Pradhan S. Comparison of low molecular weight heparin (Fragmin) with sodium heparin for prophylaxis against postoperative thrombosis in women undergoing major gynaecological surgery. Aust NZ J Obstet Gynecol 1998; 38 (1): 91–2Google Scholar
  30. 30.
    Koch MO, Smith JA. Low molecular weight heparin and radical prostatectomy: a prospective analysis of safety and side effects. Prostate Can Prost Dis 1997; 1 (2): 101–4Google Scholar
  31. 31.
    Kakkar VV, Murray WJC. Efficacy and safety of low-molecular-weight heparin (CY216) in preventing postoperative venous thrombo-embolism: a co-operative study. Br J Surg 1985; 72 (10): 786–91PubMedGoogle Scholar
  32. 32.
    The European Fraxiparin Study (EFS) Group. Comparison of a low molecular weight heparin and unfractionated heparin for the prevention of deep vein thrombosis in patients undergoing abdominal surgery. Br J Surg 1988; 75 (11): 1058–63Google Scholar
  33. 33.
    Bergqvist D, Mätzsch T, Burmark US, et al. Low molecular weight heparin given the evening before surgery compared with conventional low-dose heparin in prevention of thrombosis. Br J Surg 1988; 75 (9): 888–91PubMedGoogle Scholar
  34. 34.
    Leizorovicz A, Picolet H, Peyrieux JC, et al. Prevention of perioperative deep vein thrombosis in general surgery: a multicentre double blind study comparing two doses of Logiparin and standard heparin. Br J Surg 1991; 78 (4): 412–6Google Scholar
  35. 35.
    Caen JP. A randomized double-blind study between a low molecular weight heparin Kabi 2165 and standard heparin in the prevention of deep vein thrombosis in general surgery: a Frenchmulticenter trial. Thromb Haemost 1988; 59 (2): 216–20PubMedGoogle Scholar
  36. 36.
    Bergqvist D, Burmark US, Frisell J, et al. Low molecular weight heparin once daily compared with conventional low-dose heparin twice daily: a prospective double-blind multicentre trial on prevention of postoperative thrombosis. Br J Surg 1986; 73 (3): 204–8PubMedGoogle Scholar
  37. 37.
    Koppenhagen K, Adolf J, Matthes M, et al. Low molecular weight heparin and prevention of postoperative thrombosis in abdominal surgery. Thromb Haemost 1992; 67 (16): 627–30PubMedGoogle Scholar
  38. 38.
    Kakkar VV, Boeckl O, Boneu B, et al. Efficacy and safety of a low-molecular-weight heparin and standard unfractionated heparin for prophylaxis of postoperative venous thromboembolism: European Multicenter Trial. World J Surg 1997; 21 (1): 2–9PubMedGoogle Scholar
  39. 39.
    Wiig JN, Solhaug JH, Bilberg T, et al. Prophylaxis of venographically diagnosed deep vein thrombosis in gastrointestinal surgery: multicentre trials 20mg and 40mg enoxaparin versus dextran. Eur J Surg 1995; 161 (9): 663–8PubMedGoogle Scholar
  40. 40.
    Ockelford PA, Patterson J, Johns AS. A double-blind randomized placebo controlled trial of thromboprophylaxis in major elective general surgery using once daily injections of a low molecular weight heparin fragment (Fragmin). Thromb Haemost 1989; 62 (4): 1046–9PubMedGoogle Scholar
  41. 41.
    Bjerkeset O, Larsen S, Rejertsen O. Evaluation of enoxaparin given before and after operation to prevent venous thromboembolism during digestive surgery: play-the-winner designed study. World J Surg 1997; 21 (6): 584–9PubMedGoogle Scholar
  42. 42.
    Heilmann L, Tempelhoff GFV, Kirkpatrick C, et al. Comparison of unfractionated versus low molecular weight heparin for deep vein thrombosis prophylaxis during breast and pelvic cancer surgery: efficacy, safety, and follow-up. Clin Appl Thromb Hemost 1998; 4 (4): 268–73Google Scholar
  43. 43.
    Gondret R, Dominici L, Angelard B, et al. Safety of preoperative enoxaparin in head and neck cancer surgery. Head Neck 1995; 17 (1): 1–6PubMedGoogle Scholar
  44. 44.
    Bergqvist D, Eldor A, Thorlaciusussing O, et al. Efficacy and safety of enoxaparin versus unfractionated heparin for prevention of deep-vein thrombosis in elective cancer surgery: a double-blind randomized multicenter trial with venographic assessment. Br J Surg 1997; 84 (8): 1099–103Google Scholar
  45. 45.
    Turpie AGG, Levine MN, Hirsh J, et al. Arandomized controlled trial of a low molecular weight heparin (enoxaparin) to prevent deep-vein thrombosis in patients undergoing elective hip surgery. N Engl J Med 1986; 315 (15): 925–9PubMedGoogle Scholar
  46. 46.
    Levine MN, Hirsh J, Gent M, et al. Prevention of deep vein thrombosis after elective hip surgery: a randomized trial comparing low molecular weight heparin with standard unfractionated heparin. Ann Intern Med 1991; 114 (7): 545–51PubMedGoogle Scholar
  47. 47.
    Colwell CW, Spiro TE, Trowbridge AA, et al. Use of enoxaparin, a low molecular weight heparin, and unfractionated heparin for the prevention of deep venous thrombosis after elective hip replacement. J Bone Joint Surg 1994; 76-A (1): 3–14PubMedGoogle Scholar
  48. 48.
    Colwell CW, Spiro TE. Efficacy and safety of enoxaparin to prevent deep vein thrombosis after hip arthroplasty. Clin Orthop 1995; 319: 215–22PubMedGoogle Scholar
  49. 49.
    Colwell CW, Spiro TE, Trowbridge AA, et al. Efficacy and safety of enoxaparin versus unfractionated heparin for prevention of deep venous thrombosis after elective knee arthroplasty. Clin Orthop 1995; 321: 19–27PubMedGoogle Scholar
  50. 50.
    Faunø P, Suomalainen AO, Rehnberg V, et al. Prophylaxis for the prevention of venous thromboembolism after total knee arthroplasty: a comparison between unfractionated and low molecular- weight heparin. J Bone Joint Surg 1994; 76-A (12): 1814–8PubMedGoogle Scholar
  51. 51.
    Planès A, Vochelle N, Darmon JY, et al. Risk of deep-venous thrombosis after hospital discharge in patients having undergone total hip replacement: double-blind randomised comparison of enoxaparin versus placebo. Lancet 1996; 348 (9022): 224–8PubMedGoogle Scholar
  52. 52.
    Gallay S, Waddell JP, Cardella P, et al. A short course of low molecular- weight heparin to prevent deep venous thrombosis after elective total hip replacement. Can J Surg 1997; 40 (12): 119–23PubMedGoogle Scholar
  53. 53.
    Bergqvist D, Benoni G, Björgell O, et al. Low-molecular weight heparin (enoxaparin) as prophylaxis against venous thromboembolism after total hip replacement. N Engl J Med 1996; 335 (10): 696–700PubMedGoogle Scholar
  54. 54.
    Hull R, Raskob G, Pineo G, et al. A comparison of subcutaneous low molecular weight heparin and warfarin sodium for prophylaxis against deep-vein thrombosis after hip or knee implantation. N Engl J Med 1993; 329 (19): 1370–6PubMedGoogle Scholar
  55. 55.
    RD Heparin Arthroplasty Group. RD heparin compared with warfarin for prevention of venous thromboembolic disease following total hip or knee arthroplasty. J Bone Joint Surg 1994; 76A (8): 1174–85Google Scholar
  56. 56.
    Leclerc JR, Geerts WH, Desjardins L, et al. Prevention of deep vein thrombosis after major knee surgery: a randomized, double-blind trial comparing a low molecular weight heparin fragment (enoxaparin) to placebo. Thromb Haemost 1992; 67 (4): 417–23PubMedGoogle Scholar
  57. 57.
    Lassen MR, Borris LC, Christiansen HM, et al. Prevention of thromboembolism in 190 hip arthroplasties: comparison of LMW heparin and placebo. Acta Orthop Scand 1991; 62 (1): 33–8PubMedGoogle Scholar
  58. 58.
    Dahl OE, Andreassen G, Aspelin T, et al. Prolonged thromboprophylaxis following hip replacement surgery: results of a double-blind, prospective, randomized, placebo-controlled study with dalteparin (Fragmin). Thromb Haemost 1997; 77 (1): 26–31PubMedGoogle Scholar
  59. 59.
    Leclerc JR, Gent M, Hirsh J, et al. The incidence of symptomatic venous thromboembolism during and after prophylaxis with enoxaparin: a multi-institutional cohort study in patients who underwent hip or knee arthroplasty. Arch Intern Med 1998; 158 (8): 873–8PubMedGoogle Scholar
  60. 60.
    Leclerc JR, Geerts WH, Desjardins L, et al. Prevention of venous thromboembolism after knee arthroplasty: a randomized, double-blind trial comparing enoxaparin with warfarin. Ann Intern Med 1996; 124 (7): 619–26PubMedGoogle Scholar
  61. 61.
    Eriksson BI, Wille-Jørgensen P, Kälebo P, et al. A comparison of recombinant hirudin with low-molecular-weight heparin to prevent thromboembolic complications after total hip replacement. N Engl J Med 1997; 337 (19): 1329–35PubMedGoogle Scholar
  62. 62.
    Spiro TE, Johnson GJ, Christie MJ, et al. Efficacy and safety of enoxaparin to prevent venous thrombosis after hip replacement surgery. Ann Intern Med 1994; 121 (2): 81–9PubMedGoogle Scholar
  63. 63.
    Planès A, Vochelle N, Mazas F, et al. Prevention of postoperative venous thrombosis: a randomized trial comparing unfractionated heparin with low molecular weight heparin in patients undergoing total hip replacement. Thromb Haemost 1988; 60 (3): 407–10PubMedGoogle Scholar
  64. 64.
    Dechavanne M, Ville D, Berruyer M, et al. Randomized trial of a low-molecular-weight heparin (Kabi 2165) versus adjusted dose subcutaneous standard heparin in the prophylaxis of deep-vein thrombosis after elective hip surgery. Haemostasis 1989; 19 (1): 5–12PubMedGoogle Scholar
  65. 65.
    Leyvraz PF, Bachmann F, Hoek J, et al. Prevention of deep vein thrombosis after hip replacement: randomized comparison between unfractionated heparin and low molecular weight heparin. BMJ 1991; 303 (6802): 543–8PubMedGoogle Scholar
  66. 66.
    Heit JA, Berkowitz SD, Bona R, et al. Efficacy and safety of low molecular weight heparin (ardeparin sodium) compared to warfarin for the prevention of venous thromboembolic disease after total knee replacement surgery: a double-blind, dose ranging study. Thromb Haemost 1997; 77 (1): 32–8PubMedGoogle Scholar
  67. 67.
    Francis CW, Pellegrini VD, Totterman S, et al. Prevention of deep-vein thrombosis after total hip arthroplasty: comparison of warfarin and dalteparin. J Bone Joint Surg Am 1997; 79 (9): 1365–72PubMedGoogle Scholar
  68. 68.
    The German Hip Arthroplasty Trial (GHAT) Group. Prevention of deep vein thrombosis with low-molecular-weight heparin in patients undergoing total hip replacement: a randomized trial. Arch Orthop Trauma Surg 1992; 111 (2): 110–20Google Scholar
  69. 69.
    The Danish Enoxaparin Study Group. Low-molecular weight heparin (enoxaparin) vs dextran 70: the prevention of post operative deep vein thrombosis after total hip replacement. Arch Intern Med 1991; 151 (8): 1621–4Google Scholar
  70. 70.
    Planès A, Chastang CL, Vochelle N, et al. Comparison of antithrombotic efficacy and hemorrhagic side-effects of clivarin versus enoxaparin in patients undergoing total hip replacement surgery. Blood Coagul Fibrinolysis 1993; 4 Suppl. 1: S33–8Google Scholar
  71. 71.
    Monreal M, Lafoz E, Navarro A, et al. A prospective doubleblind trial of a low molecular weight heparin once daily compared with conventional low-dose heparin three times daily to prevent pulmonary embolism and venous thrombosis in patients with hip fracture. J Trauma 1989; 29 (6): 873–5PubMedGoogle Scholar
  72. 72.
    Jørgensen PS, Knudsen JF, Broeng L, et al. The thromboprophylactic effects of a low-molecular-weight heparin (Fragmin) in hip fracture surgery: a placebo-controlled study. Clin Orthop 1992; 278: 95–100PubMedGoogle Scholar
  73. 73.
    Barsotti J, Gruel Y, Rosset P, et al. Comparative double-blind study of two dosage regimens of low-molecular weight heparin in elderly patients with fracture of the neck of the femur. J Orthop Trauma 1990; 4 (4): 371–5PubMedGoogle Scholar
  74. 74.
    Harenberg J, Roebruck P, Heene D, et al. Subcutaneous low molecular weight heparin versus standard heparin and the prevention of thromboembolisms in medical inpatients. Haemostasis 1996; 26 (3): 127–39PubMedGoogle Scholar
  75. 75.
    Bergman JF, Neuhart E. Amulticenter randomized double-blind study of enoxaparin compared with unfractionated heparin in the prevention of venous thromboembolic disease in elderly in-patients bedridden for an acute medical illness. Thromb Haemost 1996; 76 (4): 529–34Google Scholar
  76. 76.
    Dahan R, Houlbert D, Caulin C, et al. Prevention of deep vein thrombosis in elderly medical in-patients by a low molecular weight heparin: a randomized double-blind trial. Haemostatis 1986; 16 (2): 159–64Google Scholar
  77. 77.
    Harenberg J, Kallenbach B, Martin U, et al. Randomized controlled study of heparin and low molecular weight heparin for prevention of deep-vein thrombosis in medical patients. Thromb Res 1990; 59 (3): 639–50PubMedGoogle Scholar
  78. 78.
    Lechler E, Schramm W, Flosbach CW, the Prime Study Group. The venous thrombotic risk in non-surgical patients: epidemiological data and efficacy/safety profile of a low-molecular weight heparin (enoxaparin). Haemostatis 1996; 26 Suppl. 2: 49–56Google Scholar
  79. 79.
    Sandset PM, Dahl T, Stiris M, et al. A double-blind randomized placebo-controlled trial of low molecular weight heparin once daily to prevent deep-vein thrombosis in acute ischemic stroke. Semin Thromb Hemost 1990; 16 Suppl. 1: 25–33PubMedGoogle Scholar
  80. 80.
    Prins MH, Gelsema R, Sing AK, et al. Prophylaxis of deep venous thrombosis with a low molecular weight heparin (Kabi 2165) in stroke patients. Haemostasis 1989; 19 (5): 245–50PubMedGoogle Scholar
  81. 81.
    Green D, Lee MY, Lim AC, et al. Prevention of thromboembolism after spinal cord injury using low-molecular-weight heparin. Ann Intern Med 1990; 113 (8): 571–4PubMedGoogle Scholar
  82. 82.
    Harris S, Chen D, Green D. Enoxaparin for thromboembolism prophylaxis in spinal injury: preliminary report on experience with 105 patients. Am J Phys Med Rehabil 1996; 75 (5): 326–7PubMedGoogle Scholar
  83. 83.
    Nurmohamed MT, van Riel AM, Henkens CM, et al. Low molecular weight heparin and compression stockings in the prevention of venous thromboembolism in neurosurgery. Thromb Haemost 1996; 75 (2): 233–8PubMedGoogle Scholar
  84. 84.
    Agnelli G, Piovella F, Buoncristiani P, et al. Enoxaparin plus compression stockings compared with compression stockings alone in the prevention of venous thromboembolism after elective neurosurgery. N Engl J Med 1998; 339 (12): 80–5PubMedGoogle Scholar
  85. 85.
    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): 701–7PubMedGoogle Scholar
  86. 86.
    Knudsen MM, Morabito D, Paiement GD, et al. Use of low molecular weight heparin in preventing thromboembolism in trauma patients. J Trauma 1996; 41 (3): 446–59Google Scholar
  87. 87.
    Wells PS, Kovacs MJ, Bormanis J, et al. Expanding eligibility for outpatient treatment of deep venous thrombosis and pulmonary embolism with low-molecular-weight heparin. Arch Intern Med 1998; 158 (16): 1809–12PubMedGoogle Scholar
  88. 88.
    Ting SBN, Ziegenbein RW, Gan TE, et al. Dalteparin for deep venous thrombosis: a hospital-in-the-home program. Med J Aust 1998; 168 (6): 272–6PubMedGoogle Scholar
  89. 89.
    Lensing AWA, Prins MH, Davidson BL, et al. Treatment of deep venous thrombosis with low molecular weight heparins: a meta-analysis. Arch Intern Med 1995; 155 (6): 601–7PubMedGoogle Scholar
  90. 90.
    Hirsh J, Siragusa S, Cosmi B, et al. Low molecular weight heparins (LMWH) in the treatment of patients with acute venous thromboembolism. Thromb Haemost 1995; 74 (1): 360–3PubMedGoogle Scholar
  91. 91.
    The Columbus Invetigators. Low-molecular-weight heparin in the treatment of patients with venous thromboembolism. N Engl J Med 1997; 337 (10): 657–62Google Scholar
  92. 92.
    Simonneau G, Sors H, Charbonnier B, et al. A comparison of low-molecular-weight heparin with unfractionated heparin for acute pulmonary embolism. N Engl JMed 1997; 337 (10): 663–9Google Scholar
  93. 93.
    Amann FW, Neuenschwander CH, Meyer BJ. Fraxiparin for prevention of restenosis after percutaneous transluminal coronary angioplasty. Semin Thromb Hemost 1993; 19 Suppl. 1: 160–3PubMedGoogle Scholar
  94. 94.
    Melandri G, Semprini F, Cervi V, et al. Benefit of adding low molecular weight heparin to the conventional treatment of stable angina pectoris. a double-blind, randomized, placebo-controlled trial. Circulation 1993; 88 (6): 2517–23PubMedGoogle Scholar
  95. 95.
    Gurfinkel EP, Manos EJ, Mejail RI, et al. Low molecular weight heparin versus regular heparin or aspirin in the treatment of unstable angina and silent ischemia. J Am Coll Cardiol 1995; 26 (2): 313–8PubMedGoogle Scholar
  96. 96.
    Antman EM. TIMI 11B: enoxaparin versus unfractionated heparin for unstable angina or non-Q-wave myocardial infarction. A double-blind, placebo-controlled parallel-group, multicenter trial: rationale, study design and methods. Am Heart J 1998; 135 (6 Pt 2 Suppl. 2): S353–60Google Scholar
  97. 97.
    Glick A, Kornowski R, Michowich Y, et al. Reduction of reinfarction and angina with use of low-molecular-weight heparin therapy after streptokinase (and heparin) in acute myocardial infarction. Am J Cardiol 1996; 77 (14): 1145–8PubMedGoogle Scholar
  98. 98.
    Klein W, Buchwald A, Hillis S, et al. Comparison of low molecular weight heparin with UFH acutely and with placebo for 6 weeks in the management of unstable coronary artery disease study (FRIC). Circulation 1997; 96 (1): 61–8PubMedGoogle Scholar
  99. 99.
    Cohen M, Demers C, Gurfinkel EP, et al. Low-molecular weight heparins in non-ST- segment elevation ischemia: the ESSENCE trial. Efficacy and safety of subcutaneous enoxaparin versus intravenous unfractionated heparin, in non- Q-wave Coronary Events. Am J Cardiol 1998; 82 (5B): 19L-24LGoogle Scholar
  100. 100.
    Hawkins DW, Langley PC, Krueger KP. Pharmacoeconomic model of enoxaparin versus heparin for prevention of deep vein thrombosis after total hip replacement. Am J Health Syst Pharm 1997; 54 (10): 1185–90PubMedGoogle Scholar
  101. 101.
    Anderson DR, O’Brien BJ, Levine MN, et al. Efficacy and cost of low-molecular-weight heparin compared with standard heparin for the prevention of deep vein thrombosis after total hip arthroplasty. Ann Intern Med 1993; 119 (11): 1105–12PubMedGoogle Scholar
  102. 102.
    Lloyd AC, Aitken JA, Hoffmeyer UK, et al. Economic evaluation of the use of nadroparin in the treatment of deep-vein thrombosis in Switzerland. Ann Pharmacother 1997; 31 (7–8): 842–6PubMedGoogle Scholar
  103. 103.
    Wade WE, Taylor AT, Spruill WJ. Using published, institutional data to evaluate the cost effectiveness of DVT prophylaxis. Formulary 1996; 31 (12): 1204–6, 1209–10Google Scholar
  104. 104.
    Menzin J, Richner R, Huse D, et al. Prevention of deep-vein thrombosis following total hip replacement surgery with enoxaparin versus unfractionated heparin: a pharmacoeconomic evaluation. Ann Pharmacother 1994; 28 (2): 271–5PubMedGoogle Scholar
  105. 105.
    Hull RD, Raskob GE, Pineo GF, et al. Subcutaneous low-molecular-weight heparin vs warfarin for prophylaxis of deep vein thrombosis after hip or knee implantation: an economic perspective. Arch Intern Med 1997; 157 (3): 298–303PubMedGoogle Scholar
  106. 106.
    Menzin J, Colditz GA, Regan MM. 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): 757–64PubMedGoogle Scholar
  107. 107.
    Borris LC, Lassen MR, Jensen HP. Perioperative thrombosis prophylaxis with low molecular weight heparins in elective hip surgery: clinical and economic considerations. Int J Clin Pharmacol Ther 1994; 32 (5): 262–8PubMedGoogle Scholar
  108. 108.
    Bergqvist D, Lindgren B, Mätzsch T. Comparison of the costs of preventing postoperative deep vein thrombosis with either unfractionated or low molecular weight heparin. Br J Surg 1996; 83 (11): 1548–52PubMedGoogle Scholar
  109. 109.
    Wade WE. Cost analysis of ardeparin versus enoxaparin for the prophylaxis of deep vein thrombosis after knee arthroplasty. Clin Ther 1998; 20 (2): 347–51PubMedGoogle Scholar
  110. 110.
    Mamdani MM, Weingarten CM, Stevenson JG. Thromboembolic prophylaxis in moderate-risk patients undergoing elective abdominal surgery: decision and cost-effectiveness analyses. Pharmacotherapy 1996; 16 (6): 1111–27PubMedGoogle Scholar
  111. 111.
    Hull RD, Raskob GE, Rosenbloom D, et al. Treatment of proximal vein thrombosis with subcutaneous low-molecular-weight heparin vs intravenous heparin: an economic perspective. Arch Intern Med 1997; 157 (3): 289–94PubMedGoogle Scholar
  112. 112.
    Lindmarker P, Holmstrom M, Swedish Venous Thrombosis Dalteparin Trial Group. Use of low molecular weight heparin (dalteparin) once daily for the treatment of deep vein thrombosis: a feasibility and health economic study in an outpatient setting. J Intern Med 1996; 240 (6): 395–401PubMedGoogle Scholar
  113. 113.
    Teo CP, Lim HL, Kueh YK. Cost effectiveness and ease of administration of low molecular weight heparin in deep vein thrombosis. Thromb Haemost 1994; 72 (2): 328–9PubMedGoogle Scholar
  114. 114.
    Kakkar VV. Cost-effectiveness of the low molecular weight heparin reviparin sodium in thromboprophylaxis. ThrombRes 1996; 81 (2 Suppl.): 75–7Google Scholar
  115. 115.
    Wade WE. Cost-effectiveness of venous thrombosis prophylaxis following ischemic stroke: an assessment of currently available literature. Thromb Res 1998; 89 (4): 199–202PubMedGoogle Scholar
  116. 116.
    O’Brien BJ, Anderson DR, Goeree R. Cost-effectiveness of enoxaparin versus warfarin prophylaxis against deep-vein thrombosis after hip replacement. Can Med Assoc J 1994; 150 (7): 1083–90Google Scholar
  117. 117.
    Mol WEM, Egberts TCG. Prophylaxis for venous thromboembolism in hip fracture surgery: total costs and cost effectiveness in the Netherlands. Pharmacoeconomics 1994; 5 (1): 48–55PubMedGoogle Scholar
  118. 118.
    Drummond M, Aristides M, Davies L, et al. Economic evaluation of standard heparin and enoxaparin for prophylaxis against deep vein thrombosis in elective hip surgery. Br J Surg 1994; 81 (12): 1742–6PubMedGoogle Scholar
  119. 119.
    Wade WE. Cost-effectiveness of venous thrombosis prophylaxis after ischemic stroke. Am J Phys Med Rehabil 1998; 77 (3): 267–8PubMedGoogle Scholar
  120. 120.
    Dunn CJ, Goa KL. Enoxaparin: a pharmacoeconomic appraisal of its use in thromboembolic prophylaxis after total hip arthroplasty. Pharmacoeconomics 1996; 10 (8): 179–90PubMedGoogle Scholar
  121. 121.
    Lloyd A, Aitken JA, Hoffmeyer UKO, 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 1997; 12 (4): 475–85PubMedGoogle Scholar
  122. 122.
    Detournay B, Planès A, Vochelle N. Cost effectiveness of a low-molecular-weight heparin in prolonged prophylaxis against deep vein thrombosis after total hip replacement. Pharmacoeconomics 1998; 13 (1): 81–9PubMedGoogle Scholar
  123. 123.
    Alexandrov AV, Smurawska LT, Bartle W, et al. Cost considerations in the pharmacological prevention and treatment of stroke. Pharmacoeconomics 1997; 11 (5): 408–18PubMedGoogle Scholar
  124. 124.
    Anderson DR, O’Brien BJ. Cost effectiveness of the prevention and treatment of deep vein thrombosis and pulmonary embolism. Pharmacoeconomics 1997; 12 (6): 17–29PubMedGoogle Scholar
  125. 125.
    Valette F, Hoffmeyer U, Lloyd A. Economic evaluation of the use of tinzaparin in the treatment of deep vein thrombosis. Br J Med Econ 1995; 8 (2): 111–23Google Scholar
  126. 126.
    Wade WE, Spruill WJ. Cost analysis of the American College of Chest Physicians guidelines for deep vein thrombosis prophylaxis in patients undergoing orthopedic arthroplastic surgery. Pharmacotherapy 1997; 17 (6): 1286–91PubMedGoogle Scholar
  127. 127.
    Mark D. When innovative therapies make economic sense: economic analysis of enoxaparin versus unfractionated heparin in the ESSENCE trial. An overview. Can J Cardiol 1998; 14 Suppl. E: 24–7Google Scholar
  128. 128.
    Mark DB, Cowper PA, Berkowitz SD, et al. Economic assessment of low-molecular-weight heparin (enoxaparin) versus unfractionated heparin in acute coronary syndrome patients: results from the ESSENCE randomized trial. Circulation 1998; 97 (17): 1702–5PubMedGoogle Scholar
  129. 129.
    Commonwealth Department of Human Services and Health. Guidelines for the pharmaceutical industry on preparation of submissions to the Pharmaceutical Benefits Advisory Committee: including major submissions involving economic analyses. Canberra: Australian Government Publishing Service, 1995Google Scholar
  130. 130.
    Wade WE, Spruill WJ, Taylor AT, et al. The expanding role of pharmacy and therapeutics committees: the 1990s and beyond. Pharmacoeconomics 1996; 10 (2): 123–8PubMedGoogle Scholar
  131. 131.
    Jolicoeur LM, Jones-Grizzle AJ, Boyer JG. Guidelines for performing a pharmacoeconomic analysis. Am J Hosp Pharm 1992; 49 (7): 1741–7PubMedGoogle Scholar
  132. 132.
    Sanchez LA. Pharmacoeconomic principles and methods: conducting pharmacoeconomic evaluations in a hospital setting. Hosp Pharm 1995; 30 (5): 412–28 1Google Scholar
  133. 33.
    Clemens K, Townsend R, Luscombe F, et al. Methodological and conduct principles for pharmacoeconomic research. Pharmacoeconomics 1995; 8 (2): 169–74PubMedGoogle Scholar
  134. 134.
    Bungay KM, Sanchez LA. Types of economic and humanistic outcomes assessments. In: Bungay KM, Osterhaus JT, Paladino JA, et al., editors. Pharmacoeconomics and outcomes: applications for patient care. Module 1. Kansas City (MO): American College of Clinical Pharmacy, 1996: 87–123Google Scholar
  135. 135.
    Armstrong EP. Evaluating low molecular weight heparins within a health system: issues and strategies. Formulary 1999; 34 (2): 144–8Google Scholar
  136. 136.
    Hull RD, Hirsh J, Sackett DL, et al. Cost-effectiveness of primary and secondary prevention of fatal pulmonary embolism in high-risk surgical patients. Can Med Assoc J 1982; 127 (10): 990–5PubMedGoogle Scholar
  137. 137.
    Cost-effectiveness analysis. In: Drummond MF, O’Brien B, Stoddart GL, et al., editors. Methods for the economic evaluation of health care programmes. New York (NY): Oxford University Press, Inc., 1997: 96–138Google Scholar
  138. 138.
    Oster G, Tuden RL, Colditz GA. A cost-effectiveness analysis of prophylaxis against deep vein thrombosis in major orthopedic surgery. JAMA 1987; 257 (2): 203–8PubMedGoogle Scholar
  139. 139.
    Bergqvist D, Mätzsch T. Cost/benefit aspects of thromboprophylaxis. Haemostasis 1993; 23 Suppl. 1: 15–9PubMedGoogle Scholar
  140. 140.
    Sarasin FP, Bounameaux H. Cost-effectiveness of prophylactic anticoagulation prolonged after hospital discharge following general surgery. Arch Surg 1996; 131 (7): 694–7PubMedGoogle Scholar

Copyright information

© Adis International Limited 2000

Authors and Affiliations

  • William E. Wade
    • 1
  • Bradley C. Martin
    • 1
  • Jeffrey A. Kotzan
    • 1
  • William J. Spruill
    • 1
  • Marie A. Chisoholm
    • 1
  • Matthew Perri
    • 1
  1. 1.College of PharmacyUniversity of GeorgiaAthensUSA

Personalised recommendations