Hostname: page-component-78c5997874-xbtfd Total loading time: 0 Render date: 2024-11-10T05:18:28.917Z Has data issue: false hasContentIssue false
  • English
  • Français

Low-molecular-weight heparins: Pharmacoeconomic decision modeling based on meta-analysis data

Published online by Cambridge University Press:  29 June 2010

Edmundas Kadusevicius ,
Gabriele Kildonaviciute ,
Birute Varanaviciene  and
Danguole Jankauskiene
Edmundas Kadusevicius
Affiliation:
Kaunas Medical University and Kaunas Medical University Hospital
Gabriele Kildonaviciute
Affiliation:
Kaunas Medical University and Quintiles, JSC
Birute Varanaviciene
Affiliation:
Kaunas Medical University Hospital
Danguole Jankauskiene
Affiliation:
Mykolas Romeris University
Get access Rights & Permissions [Opens in a new window]

Abstract

Objectives: The aim of this study was to compare efficacy, safety, and consumption of low-molecular-weight heparins with unfractionated heparin, and to develop a pharmacoeconomic decision model based on meta-analysis data.

Methods: Review and meta-analysis were performed of published randomized control trials directly comparing the safety and efficacy of low-molecular-weight heparins (LMWHs)—that is, nadroparin, enoxaparin, and dalteparin—and unfractionated heparin (UFH) was performed by two reviewers using inclusion/exclusion criteria based on the research objectives. The value of fixed effects and random effects odds ratio (95 percent confidence interval) was calculated for each trial for the composite end point. Subsequently, a pharmacoeconomic decision modeling based on reference pricing methodology was implemented.

Results: In comparison to UFH, all LMWHs have independently demonstrated greater safety and effectiveness. None of the LMWHs demonstrated a significant superiority over each other; therefore, the group of LMWHs was interchangeable and suitable for cost minimization analysis and reference price implementation. Being the least expensive option, dalteparin single DDD price was set as the reference. Introduction of reference pricing for LMWHs would decrease the total expenditure on LMWHs of approximately 30 percent and would result in total savings of 1.830–2.070 thousand LTL in the country of Lithuania (approximately 0.8 million USD) per year.

Conclusions: The meta-analysis results of LMWHs could be used to support a policy on reference-based pricing and pharmacoeconomic decision modeling in healthcare institutions, which would allow a decrease in healthcare expenditures.

Keywords

Meta-analysisLow-molecular-weight heparins (LMWHs)Unfractionated heparin (UFH)Reference pricingCost-minimization
Type
ASSESSMENTS
Information
International Journal of Technology Assessment in Health Care , Volume 26 , Issue 3 , July 2010 , pp. 272 - 279
Copyright
Copyright © Cambridge University Press 2010

Access options

Get access to the full version of this content by using one of the access options below. (Log in options will check for institutional or personal access. Content may require purchase if you do not have access.)

References

REFERENCES

1. Aaserud, M, Dahlgren, AT, Kösters, JP, et al. Pharmaceutical policies: Effects of reference pricing, other pricing, and purchasing policies. Cochrane Database of Syst Rev. 2006;2:CD005979.Google Scholar
2. Agnelli, G, Piovella, F, Buoncristiani, P. Enoxaparin plus compression stockings compared with compression stockings alone in the prevention of venous thromboembolism after elective neurosurgery. N Engl J Med. 1998;339:80–85.CrossRefGoogle ScholarPubMed
3. Antman, EM, Morrow, DA, McCabe, CH, et al. Enoxaparin versus unfractionated heparin with fibrinolysis for ST-elevation myocardial infarction. N Engl J Med. 2006 Apr 6;354 (14):1477–88. Epub 2006 Mar 14.Google Scholar
4. Arenas-Guzman, R, Tosti, A, Hay, R, et al. National Institute for Clinical Excellence. Pharmacoeconomics-an aid to better decision-making. J Eur Acad Dermatol Venereol. 2005;19 (Suppl 1):34–39.Google Scholar
5. Belcaro, G, Nicolaides, AN, Cesarone, MR, et al. Comparison of low-molecular-weight heparin, administered primarily at home, with unfractionated heparin, administered in hospital, and subcutaneous heparin, administered at home for deep-vein thrombosis. Angiology. 1999 Oct;50 (10):781–7.Google Scholar
6. Bounameaux, H, Huber, O, Khabiri, E, et al. Unexpectedly high rate of phlebographic deep venous thrombosis following elective general abdominal surgery among patients given prophylaxis with low-molecular-weight heparin. Arch Surg. 1993 Mar;128 (3):326–8.Google Scholar
7. Bozovich, GE, Gurfinkel, EP, Antman, EM, et al. Superiority of enoxaparin versus unfractionated heparin for unstable angina/non-Q-wave myocardial infarction regardless of activated partial thromboplastin time. Am Heart J. 2000 Oct;140 (4):637–42.CrossRefGoogle ScholarPubMed
8. Burotto, M, Gabrielli, L, Crossley, N. Critical appraisal: Subcutaneous adjusted-dose unfractionated heparin vs fixed-dose low-molecular-weight heparin in the initial treatment of venous thromboembolism. Arch Intern Med 2004; 164: 1077–83.Google Scholar
9. Chiou-Tan, FY, Garza, H, Chan, KT, et al. Comparison of dalteparin and enoxaparin for deep venous thrombosis prophylaxis in patients with spinal cord injury. Am J Phys Med Rehabil. 2003 Sep;82 (9):678–85.Google Scholar
10. Chong, BH, Brighton, TA, Baker, RI, et al. Once-daily enoxaparin in the outpatient setting versus unfractionated heparin in hospital for the treatment of symptomatic deep-vein thrombosis. J Thromb Thrombolysis. 2005 Jun;19 (3):173–81.CrossRefGoogle ScholarPubMed
11. Cohen, M, Gensini, GF, Maritz, F, et al. The safety and efficacy of subcutaneous enoxaparin versus intravenous unfractionated heparin and tirofiban versus placebo in the treatment of acute ST-segment elevation myocardial infarction patients ineligible for reperfusion (TETAMI): a randomized trial. J Am Coll Cardiol. 2003 Oct 15;42 (8):1348–56.CrossRefGoogle ScholarPubMed
12. Cohen, M, Theroux, P, Borzak, S, et al. Randomized double-blind safety study of enoxaparin versus unfractionated heparin in patients with non-ST-segment elevation acute coronary syndromes treated with tirofiban and aspirin: the ACUTE II study. The Antithrombotic Combination Using Tirofiban and Enoxaparin. Am Heart J. 2002 Sep;144 (3):470–7.Google Scholar
13. Colwell, CW Jr, Spiro, TE, Trowbridge, AA, et al. Efficacy and safety of enoxaparin versus unfractionated heparin for prevention of deep venous thrombosis after elective knee arthroplasty. Enoxaparin Clinical Trial Group. Clin Orthop Relat Res. 1995 Dec;(321):19–27.Google Scholar
14. de Lemos, JA, Blazing, MA, Wiviott, SD, et al. Enoxaparin versus unfractionated heparin in patients treated with tirofiban, aspirin and an early conservative initial management strategy: results from the A phase of the A-to-Z trial. Eur Heart J. 2004 Oct;25 (19):1688–94.Google Scholar
15. Egger, B, Schmid, SW, Naef, M, et al. Efficacy and safety of weight-adapted nadroparin calcium vs. heparin sodium in prevention of clinically evident thromboembolic complications in 1,190 general surgical patients. Dig Surg. 2000;17 (6):602–609.Google Scholar
16. Engberg, S. Systemic review and meta-analysis: Studies of studies. J Wound Ostomy Continence Nurs. 2008;35:258–265.Google Scholar
17. ENOXACAN Study Group. Efficacy and safety of enoxaparin versus unfractionated heparin for prevention of deep vein thrombosis in elective cancer surgery: a double-blind randomized multicentre trial with venographic assessment. Br J Surg. 1997 Aug;84 (8):1099–103.Google Scholar
18. Findik, S, Erkan, ML, Selcuk, MB, et al. Low-molecular-weight heparin versus unfractionated heparin in the treatment of patients with acute pulmonary thromboembolism. Respiration. 2002;69 (5):440–4.Google Scholar
19. Fitchett, DH, Langer, A, Armstrong, PW, Tan, M, et al. Randomized evaluation of the efficacy of enoxaparin versus unfractionated heparin in high-risk patients with non-ST-segment elevation acute coronary syndromes receiving the glycoprotein IIb/IIIa inhibitor eptifibatide. Long-term results of the Integrilin and Enoxaparin Randomized Assessment of Acute Coronary Syndrome Treatment (INTERACT) trial. Am Heart J. 2006 Feb;151 (2):373–9.CrossRefGoogle ScholarPubMed
20. Godoy, I, Herrera, C, Zapata, C, et al. Comparison of low-molecular-weight heparin and unfractionated heparin in the treatment of unstable angina. Rev Med Chil. 1998 Mar;126 (3):259–64.Google ScholarPubMed
21. Goodman, SG, Cohen, M, Bigonzi, F, et al. Randomized trial of low molecular weight heparin (enoxaparin) versus unfractionated heparin for unstable coronary artery disease: one-year results of the ESSENCE Study. Efficacy and Safety of Subcutaneous Enoxaparin in Non-Q Wave Coronary Events; J Am Coll Cardiol. 2000 Sep;36 (3):693–8.CrossRefGoogle ScholarPubMed
22. Goodman, SG, Fitchett, D, Armstrong, PW, Tan, M, Langer, A; Integrilin and Enoxaparin Randomized Assessment of Acute Coronary Syndrome Treatment (INTERACT) Trial Investigators., Randomized evaluation of the safety and efficacy of enoxaparin versus unfractionated heparin in high-risk patients with non-ST-segment elevation acute coronary syndromes receiving the glycoprotein IIb/IIIa inhibitor eptifibatide; Circulation. 2003 Jan 21;107 (2):238–44.CrossRefGoogle Scholar
23. Gurfinkel, EP, Manos, EJ, Mejail, RI, Cerda, MA, Duronto, EA, Garcia, CN, Daroca, AM, Mautner, B., Low molecular weight heparin versus regular heparin or aspirin in the treatment of unstable angina and silent ischemia; J Am Coll Cardiol. 1995 Aug;26 (2):313–8.CrossRefGoogle ScholarPubMed
24. Guyton, AC, Hall, JE. Textbook of medical physiology. Elsevier: Saunders; 2006:464.Google Scholar
25. Hafeli, R, Kraljevic, S, Wehrli, C, Goede, J, Conen, D., Low molecular weight heparin (dalteparin) in treatment of patients with thromboembolism incidents; Praxis (Bern 1994). 2001 Aug 16;90 (33):1339–45.Google Scholar
26. Hartl, P, Brucke, P, Dienstl, E, et al. Prophylaxis of thromboembolism in general surgery: comparison between standard heparin and Fragmin; Thromb Res. 1990 Feb 15;57 (4):577–84.CrossRefGoogle ScholarPubMed
27. Hoffman, MJ, Shah, ND, Vermeulen, LC et al. , Projecting future drug expenditures – 2004. Am J Health Syst Pharm. 2004 February.CrossRefGoogle Scholar
28. Holmstrom, M, Aberg, W, Lockner, D, Paul, C. Long-term clinical follow-up in 265 patients with deep venous thrombosis initially treated with either unfractionated heparin or dalteparin: a retrospective analysis. Thromb Haemost. 1999 Oct;82 (4):1222–6.Google ScholarPubMed
29. Hong, YJ, Jeong, MH, Lee, SH, et al. The use of low molecular weight heparin to predict clinical outcome in patients with unstable angina that had undergone percutaneous coronary intervention. Korean J Intern Med. 2003 Sep;18 (3):167–73.Google Scholar
30. Klein, W, Buchwald, A, Hillis, SE, et al. Comparison of low-molecular-weight heparin with unfractionated heparin acutely and with placebo for 6 weeks in the management of unstable coronary artery disease. Fragmin in unstable coronary artery disease study (FRIC). Circulation. 1997 Jul 1;96 (1):61–8.CrossRefGoogle ScholarPubMed
31. Koopman, MM, Prandoni, P, Piovella, F, et al. Treatment of venous thrombosis with intravenous unfractionated heparin administered in the hospital as compared with subcutaneous low-molecular-weight heparin administered at home. The Tasman Study Group. N Engl J Med. 1996 Mar 14;334 (11):682–7.CrossRefGoogle ScholarPubMed
32. Lindmarker, P, Holmstrom, M, Granqvist, S, et al. Comparison of once-daily subcutaneous Fragmin with continuous intravenous unfractionated heparin in the treatment of deep vein thrombosis; Thromb Haemost. 1994 Aug;72 (2):186–90.Google Scholar
33. Luomanmaki, K, Grankvist, S, Hallert, C, et al. A multicentre comparison of once-daily subcutaneous dalteparin (low molecular weight heparin) and continuous intravenous heparin in the treatment of deep vein thrombosis. J Intern Med. 1996 Aug;240 (2):85–92.CrossRefGoogle ScholarPubMed
34. Madan, M, Radhakrishnan, S, Reis, M, et al. Comparison of enoxaparin versus heparin during elective percutaneous coronary intervention performed with either eptifibatide or tirofiban (the ACTION Trial). Am J Cardiol. 2005 Jun 1;95 (11):1295–301.Google Scholar
35. Malhotra, S, Karan, RS, Bhargava, VK, et al. A meta-analysis of controlled clinical trials comparing low-molecular weight heparins with unfractionated heparin in unstable angina. Indian Heart J. 2001;53:197–202.Google Scholar
36. Miraldo, M. Reference pricing and firms’ pricing strategies. J Health Econ. 2009;28:176–197.CrossRefGoogle ScholarPubMed
37. Montalescot, G, Bal-dit-Sollier, C, Chibedi, D, et al. Comparison of effects on markers of blood cell activation of enoxaparin, dalteparin, and unfractionated heparin in patients with unstable angina pectoris or non-ST-segment elevation acute myocardial infarction (the ARMADA study). Am J Cardiol. 2003 Apr 15;91 (8):925–30.Google Scholar
38. Moreno-Palomares, JJ, Fisac-Herrero, RM, Herrero-Domingo, A, et al. Low molecular weight heparin versus unfractionated heparin in the treatment of deep vein thrombosis. An Med Interna. 2001 Jul;18 (7):364–8.Google Scholar
39. Ngorsuraches, S. Defining types of economic evaluation. J Med Assoc Thai. 2008;91 (Suppl 2):S21–S27.Google Scholar
40. Official website of Kaunas Medical University Hospital. www.kmuk.lt (accessed on August 17, 2009).Google Scholar
41. Okmen, E, Ozen, E, Uyarel, H, et al. Effects of enoxaparin and nadroparin on major cardiac events in high-risk unstable angina treated with a glycoprotein IIb/IIIa inhibitor. Jpn Heart J. 2003 Nov; 44 (6):899–906.Google Scholar
42. Ozdemir, M, Erdem, G, Turkoglu, S, et al. Head-to-head comparison of two different low-molecular-weight heparins in acute coronary syndrome: a single center experience. Jpn Heart J. 2002 Sep;43 (5):433–42.CrossRefGoogle ScholarPubMed
43. Richter, A. Assessing the impact of global price interdependencies. Pharmacoeconomics. 2008;26:649–659.Google Scholar
44. Ross, AM, Molhoek, P, Lundergan, C, et al. Randomized comparison of enoxaparin, a low-molecular-weight heparin, with unfractionated heparin adjunctive to recombinant tissue plasminogen activator thrombolysis and aspirin: second trial of Heparin and Aspirin Reperfusion Therapy (HART II). Circulation. 2001 Aug 7;104 (6):648–52.Google Scholar
45. Shafiq, N, Malhotra, S, Pandhi, P, et al. A Randomized Controlled Clinical Trial to Evaluate the Efficacy, Safety, Cost-Effectiveness and Effect on PAI-1 Levels of the Three Low-Molecular-Weight Heparins – Enoxaparin, Nadroparin and Dalteparin. Pharmacology 2006;78:136–143.CrossRefGoogle ScholarPubMed
46. Simonneau, G, Laporte, S, Mismetti, P, et al. A randomized study comparing the efficacy and safety of nadroparin 2850 IU (0.3 mL) vs. enoxaparin 4000 IU (40 mg) in the prevention of venous thromboembolism after colorectal surgery for cancer. J Thromb Haemost. 2006 Aug;4 (8):1693–700. Epub 2006 Jun 21.CrossRefGoogle ScholarPubMed
47. Simonneau, G, Sors, H, Charbonnier, B, et al. A comparison of low-molecular-weight heparin with unfractionated heparin for acute pulmonary embolism. The THESEE Study Group. Tinzaparine ou Heparine Standard: Evaluations dans l'Embolie Pulmonaire. N Engl J Med. 1997 Sep 4;337 (10):663–9.CrossRefGoogle Scholar
48. Sirenko, IuN, Sychev, OS, Reiko, MN, et al. The initial experience of using fraxiparin in extracorporeal detoxication in clinical cardiology. Klin Khir. 1994;(12):23–5.Google Scholar
49. Spinal Cord Injury Thromboprophylaxis Investigators. Prevention of venous thromboembolism in the rehabilitation phase after spinal cord injury: prophylaxis with low-dose heparin or enoxaparin. J Trauma. 2003 Jun;54 (6):1111–5.Google Scholar
50. Spinal Cord Injury Thromboprophylaxis Investigators. Prevention of venous thromboembolism in the acute treatment phase after spinal cord injury: a randomized, multicenter trial comparing low-dose heparin plus intermittent pneumatic compression with enoxaparin. J Trauma. 2003 Jun;54 (6):1116–24; discussion 1125–6.Google Scholar
51. Sprague, S, Quigley, L, Adili, A, et al. Understanding cost effectiveness: Money matters? J Long Term Eff Med Implants. 2007;17:145–152.Google Scholar
52. Stargardt, T, Schreyögg, J, Busse, R. Pharmaceutical reference pricing in Germany: Definition of therapeutic groups, price setting through regression procedure and effects. Gesundheitswesen. 2005;67:468–477.Google Scholar
53. Stephenson, MD, Ballem, PJ, Tsang, P, et al. Treatment of antiphospholipid antibody syndrome (APS) in pregnancy: a randomized pilot trial comparing low molecular weight heparin to unfractionated heparin; J Obstet Gynaecol Can. Aug;26 (8):729–34.Google Scholar
54. 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. 1998 Nov;75 (11):1058–63.Google Scholar
55. The FRAX.I.S. Study Group. Comparison of two treatment durations (6 days and 14 days) of a low molecular weight heparin with a 6-day treatment of unfractionated heparin in the initial management of unstable angina or non-Q wave myocardial infarction: FRAX.I.S. (FRAxiparine in Ischaemic Syndrome). Eur Heart J. 1999 Nov;20 (21):1553–62.Google Scholar
56. Wallentin, L, Bergstrand, L, Dellborg, M, et al. Low molecular weight heparin (dalteparin) compared to unfractionated heparin as an adjunct to rt-PA (alteplase) for improvement of coronary artery patency in acute myocardial infarction-the ASSENT Plus study. Eur Heart J. 2003 May;24 (10):897–908.Google Scholar
57. 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 N Z J Obstet Gynaecol. 1998 Feb;38 (1):91–2.CrossRefGoogle ScholarPubMed
Supplementary material: File

Kadusevicius et al. supplementary material

Supplementary tables

Download Kadusevicius et al. supplementary material(File)
File 140.3 KB