Skip to main content
SpringerLink
Log in

Cost Effectiveness of Enoxaparin as Prophylaxis against Venous Thromboembolic Complications in Acutely Ill Medical Inpatients

Modelling Study from the Hospital Perspective in Germany

  • Original Research Article
  • Published:
PharmacoEconomics Aims and scope Submit manuscript

Abstract

Objective: To estimate, from the hospital perspective in Germany, the cost effectiveness of the low-molecular-weight heparin (LMWH) subcutaneous enoxaparin sodium 40mg once daily (ENOX) relative to no pharmacological prophylaxis (NPP) and relative to subcutaneous unfractionated heparin (UFH) 5000IU three times daily (low-dose UFH [LDUFH]). Each is used in addition to elastic bandages/compression stockings and physiotherapy in the prevention of venous thromboembolic events (VTE) in immobilised acutely ill medical inpatients without impaired renal function or extremes of body weight.

Methods: The incremental cost-effectiveness ratios (ICERs) of the ‘additional cost for ENOX per clinical VTE avoided versus NPP’ and ‘additional cost for ENOX per episode of major bleeding avoided versus LDUFH’ were chosen as target variables. The target variables were quantified using a modelling approach based on the decision-tree technique. Resource use during thromboprophylaxis, diagnosis and treatment of VTEs, episode of major bleeding and secondary pneumonia after pulmonary embolism (PE) was collected from a hospital survey. Costs were exclusively those to hospitals incurred by staff expenses, drugs, devices, disposables, laboratory tests and equipment for diagnostic procedures. These costs were determined by multiplying utilised resource items by the price or tariff of each item as of the first quarter of 2003.

Safety and efficacy values of the comparators were taken from the MEDENOX (prophylaxis in MEDical patients with ENOXaparin) and the THE-PRINCE (THromboEmbolism-PRevention IN Cardiac or respiratory disease with Enoxaparin) trials and from a meta-analysis. The evaluation encompassed 8 (6–14) days of thromboprophylaxis plus time to treat VTE and episode of major bleeding in hospital. Point estimates of all model parameters were applied exclusively in the base-case analysis.

Results: There were incremental costs of €1106 for ENOX per clinical VTE avoided versus NPP (€1 ≈ $US1.07; average of the first quarter of 2003). ENOX dominated LDUFH: cost savings of €55 825 were obtained and 7.7 episodes of major bleeding were avoided by ENOX compared with LDUFH, each per 1000 patients. In comprehensive sensitivity analyses, the robustness of the model and its results was shown.

Conclusions: Results of this evaluation suggest that, in immobilised acutely ill medical inpatients, ENOX may offer hospitals in Germany a very cost-effective option for thromboprophylaxis compared with NPP and a cost-saving alternative compared with LDUFH.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Table I
Fig. 1
Table II
Table III
Table IV
Table V
Table VI
Table VII
Fig. 2
Fig. 3
Table VIII

Similar content being viewed by others

Notes

  1. 1 Appendices A, B and C are in the supplementary material to this article, which is listed as ‘ArticlePlus’ and can be found with the electronic version of this article on AdisOnline (http://www.AdisOnline.com/phe).

References

  1. Sandler DA, Martin IF. Autopsy proven pulmonary embolism in hospital patients: are we detecting enough deep vein thrombosis? J R Soc Med 1989; 82: 203–205

    PubMed  CAS  Google Scholar 

  2. Haas S, Haas P. Niedermolekulare Heparine. Die Anwendung in Klinik und Praxis. 2. Auflage. Steinen: ZETT-Verlag, 1999

    Google Scholar 

  3. Samama MM, Cohen AT, Dannon JY, et al. A comparison of enoxaparin with placebo for the prevention of venous thromboembolism in acutely ill medical patients. The Prophylaxis in Medical Patients with Enoxaparin Study Group. N Engl J Med 1999; 341: 793–800

    Article  PubMed  CAS  Google Scholar 

  4. Hirsh J, Hoak J. Management of deep vein thrombosis and pulmonary embolism. Circulation 1996; 93: 2212–2245

    Article  PubMed  CAS  Google Scholar 

  5. Bergqvist D, Jendteg S, Johansen L, et al. Cost of long-term complications of deep venous thrombosis of the lower extremities: an analysis of a defined population in Sweden. Ann Intern Med 1997; 126: 454–457

    PubMed  CAS  Google Scholar 

  6. Schädlich PK, Brecht JG, Huppertz E. Treatment costs of venous thromboembolic complications in acutely ill medical patients in Germany. Perfusion 2003; 16: 141–152

    Google Scholar 

  7. Gesetz zur Einführung des diagnose-orientierten Fallpauschalensystems für Krankenhäuser (Fallpauschalengesetz — FPG) vom 23. April 2002. BGBl I 2002: 1412-37

  8. Kleber FX, Witt C, Vogel G, et al. Randomized comparison of enoxaparin with unfractionated heparin for the prevention of venous thromboembolism in medical patients with heart failure or severe respiratory disease: THE-PRINCE Study Group. Am Heart J 2003; 145: 614–621

    Article  PubMed  CAS  Google Scholar 

  9. Weitz IT. Low-molecular-weight heparins. N Engl J Med 1997; 337: 688–698

    Article  PubMed  CAS  Google Scholar 

  10. Mismetti P, Laporte-Simitsidis S, Tardy B, et al. Prevention of venous thromboembolism in internal medicine with unfractionated or low-molecular-weight heparins: a meta-analysis of randomised clinical trials. Thromb Haemost 2000; 83: 14–19

    PubMed  CAS  Google Scholar 

  11. Schädlich PK, Kämmerer W, Kentsch M, et al. Wirtschaftlichkeit der Prophylaxe thromboembolischer Komplikationen mit Enoxaparin bei internistischen Patienten: Einfluss auf die Kostensituation im Krankenhaus. Krankenhauspharmazie 2004; 25: 316–325

    Google Scholar 

  12. Bundesinstitut für Arzneimittel und Medizinprodukte — BfArM (Federal Institute for Drugs and Medical Devices, the German pharmaceutical regulatory authority). Zulassungsbescheid der Indikationserweiterung für Clexane® 40 mg und für Clexane® multidose 100mg/ml zur Primärprophylaxe tiefer Venenthrombose bei nicht-chirurgischen Patienten. Bonn: BfArM, 2000 March

    Google Scholar 

  13. Lamy A, Wang X, Kent R, et al. Economic evaluation of the MEDENOX trial: a Canadian perspective. Can Respir J 2002; 9: 169–177

    PubMed  Google Scholar 

  14. Pechevis M, Detournay B, Pribil C, et al. Economic evaluation of enoxaparin vs placebo for the prevention of venous thromboembolism in acutely ill medical patients. Value Health 2000; 3: 389–396

    Article  PubMed  CAS  Google Scholar 

  15. Nuijten MJC, Villar Antofianzas F, Kosa J, et al. Cost-effectiveness of enoxaparin as thromboprophylaxis in acutely ill medical patients in Spain. Value Health 2003; 6: 126–136

    Article  PubMed  CAS  Google Scholar 

  16. Lloyd AC, Anderson PM, Quinlan DJ, et al. Economic evaluation of the use of enoxaparin for thromboprophylaxis in acutely ill medical patients. J Med Econ 2001; 4: 99–113

    Article  Google Scholar 

  17. de Lissovoy G, Subedi P. Economic evaluation of enoxaparin as prophylaxis against venous thromboembolism in seriously ill medical patients: a US perspective. Am J Manag Care 2002; 8: 1082–1088

    PubMed  Google Scholar 

  18. Tutpie AG. Thrombosis prophylaxis in the acutely ill medical patient: insights from the Prophylaxis in MEDical patients with ENOXaparin (MEDENOX) trial. Am J Cardiol 2000; 86 (12B): 48M–52M

    Google Scholar 

  19. Brecht JG, Jenke A, Köhler ME, et al für den Arbeitskreis Pharmakoökonomie der Deutschen Gesellschaft für Klinische Pharmakologie und Therapie eV. Empfehlungen der Deutschen Gesellschaft für Klinische Phamakologie und Therapie zur Durchführung und Bewertung pharmakoökonomischer Studien. Med Klin 1995; 90: 541–546

    CAS  Google Scholar 

  20. Bundesministerium des Innern — BMI. Bundes-Angestelltentarifvertrag (BAT) vom 23. Februar 1961, zuletzt geändert durch 78. Änderungstarifvertrag vom 31. Januar 2003. Berlin: BMI, 2003

    Google Scholar 

  21. Schönfeld W. Lexikon für das Lohnbüro — Ausgabe 2003. Arbeitslohn, Lohnsteuer und Sozialversicherung von A–Z. 45. Auflage. München: Jehle Rehm, 2003

    Google Scholar 

  22. Gebührenordnung für Ärzte (GOÄ). Stand der Ausgabe 1.1.2003. Köln: Deutscher Ärzte-Verlag, 2003

    Google Scholar 

  23. Oster G, Tuden RL, Colditz GA. A cost-effectiveness analysis of prophylaxis against deep-vein-thrombosis in major orthopaedic surgery. JAMA 1987; 257: 203–208

    Article  PubMed  CAS  Google Scholar 

  24. Oster G, Tuden RL, Colditz GA. Prevention of venous thromboembolism after general surgery: cost-effectiveness analysis of alternative approaches to prophylaxis. Am J Med 1987; 82: 889–899

    Article  PubMed  CAS  Google Scholar 

  25. Detournay B, Planes A, Vochelle N, et al. Cost effectiveness of a low-molecular-weight heparin in prolonged prophylaxis against deep vein thrombosis after total hip replacement. Pharmacoeconomics 1998; 13 (1 Pt 1): 81–89

    Article  PubMed  CAS  Google Scholar 

  26. Attanasio E, Russo P, Carunchio G, et al. Dermatan sulfate versus unfractionated heparin for the prevention of venous thromboembolismin patients undergoing surgery for cancer: a cost-effectiveness analysis. Pharmacoeconomics 2001; 19: 57–68

    Article  PubMed  CAS  Google Scholar 

  27. Wood KE. Major pulmonary embolism: review of a pathophysiologic approach to the golden hour of hemodynamically significant pulmonary embolism. Chest 2002; 121: 877–905

    Article  PubMed  Google Scholar 

  28. Dalen JE. Pulmonary embolism: what have we learned since Virchow? Treatment and prevention. Chest 2002; 122: 1801–1817

    Article  PubMed  Google Scholar 

  29. Elliott CG, Goldhaber SZ, Visani L, et al. Chest radiographs in acute pulmonary embolism: results from the International Cooperative Pulmonary Embolism Registry. Chest 2000; 118: 33–38

    Article  PubMed  CAS  Google Scholar 

  30. Alexander JK. Pulmonary embolism. In: Beers MH, Berkow R, editors. The Merck manual of diagnosis and therapy. 17th ed. Whitehouse Station (NJ): Merck & Co Inc, 2003: Chapter 72 [online]. Available from URL: http://www.merck.com/pubs/mmanual/section6/chapter72n2a.htm [Accessed 2003 Mar 6]

    Google Scholar 

  31. Levine MN, Raskob G, Landefeld S, et al. Hemorrhagic complications of anticoagulant treatment. Chest 2001; 119: 108S–121S

    Article  PubMed  CAS  Google Scholar 

  32. Levine MN. Thrombolytic therapy for venous thromboembolism. Clin Chest Med 1995; 16: 321–328

    PubMed  CAS  Google Scholar 

  33. Agnelli G, Becattini C, Kirschstein T. Thrombolysis vs heparin in the treatment of pulmonary embolism: a clinical outcome-based meta-analysis. Arch Intern Med 2002; 162: 2537–2541

    Article  PubMed  CAS  Google Scholar 

  34. Gould MK, Dembitzer AS, Doyle RL, et al. Low-molecularweight heparins compared with unfractionated heparin for treatment of acute deep venous thrombosis: a meta-analysis of randomized, controlled trials. Ann Intern Med 1999; 130: 800–809

    PubMed  CAS  Google Scholar 

  35. Douketis JD, Kearon C, Bates S, et al. Risk of fatal pulmonary embolism in patients with treated venous thromboembolism. JAMA 1998; 279: 458–462

    Article  PubMed  CAS  Google Scholar 

  36. Kearon C, Julian JA, Newman IE, et al. Noninvasive diagnosis of deep vein thrombosis. Ann Intern Med 1998; 128: 663–667

    PubMed  CAS  Google Scholar 

  37. de Valois JC, van Schaik CC, Verzijlbergen F, et al. Contrast venography: from gold standard to ‘golden backup’ in clinically suspected deep vein thrombosis. Eur J Radiol 1990; 11: 131–137

    Article  PubMed  Google Scholar 

  38. Deutsche Gesellschaft für Angiologie, Gesellschaft für Gefäßmedizin. Leitlinien zur Diagnostik und Therapie der Venenthrormose und Lungenembolie. Stand Januar 2002. VASA 2002; 31 Suppl. 60: 1–19

    Google Scholar 

  39. Torbicki A, van Beek EJR, et al. Task force report: guidelines on diagnosis and management of acute pulmonary embolism. European Society of Cardiology Task Force on Pulmonary Embolism. Eur Heart J 2000; 21: 1301–1336

    Article  Google Scholar 

  40. Selvin S. Statistical analysis of epidemiologic data. 2nd ed. New York: Oxford University Press, 1996

    Google Scholar 

  41. Drummond MF, O’Brien B, Stoddart GL, et al. Methods for the economic evaluation of healthcare programmes. 2nd ed. Oxford (UK): Oxford University Press, 1997

    Google Scholar 

  42. Bronstein IN, Semendjajew KA, Grosche G, et al. Teubnertaschenbuch der mathematik. Stuttgart: Teubner, 1996

    Google Scholar 

  43. Schädlich PK, Brecht JG. The cost effectiveness of acamprosate in the treatment of alcoholism in Germany: economic evaluation of the prevention of relapse with acamprosate in the management of alcoholism (PRAMA) study. Pharmacoeconomics 1998; 13 (6): 719–730

    Article  PubMed  Google Scholar 

  44. Schädlich PK, Huppertz E, Brecht JG. Cost-effectiveness analysis of ramipril in heart failure after myocardial infarction: economic evaluation of the Acute Infarction Ramipril Efficacy (AIRE) study for Germany from the perspective of statutory health insurance. Pharmacoeconomics 1998; 14 (6): 654–669

    Google Scholar 

  45. Schädlich PK, Brecht JG. Economic evaluation of specific immunotherapy versus symptomatic treatment of allergic rhinitis in Germany. Pharmacoeconomics 2000; 17 (1): 37–52

    Article  PubMed  Google Scholar 

  46. Kleijnen JPC, van Groenendal W. Simulation: a statistical perspective. Chichester: John Wiley & Sons, 1992

    Google Scholar 

  47. Fishman G. Monte Carlo: concepts, algorithms, and applications. New York: Springer, 1996

    Google Scholar 

  48. Hartung J, Elpelt B, Klosener KH. Statistik: Lehr- und Handbuch der angewandten Statistik. 13. Auflage. München: Oldenbourg, 2002

    Google Scholar 

  49. Bergmann JF, Neuhart E. A multicenter randomized doubleblind study of enoxaparin cOfIllared with unfractionated heparin in the prevention of venous thromboembolic disease in elderly in-patients bedridden for an acute medical illness: from the Enoxaparin in Medicine Study Group (EMSG). Thromb Haemost 1996; 76: 529–534

    PubMed  CAS  Google Scholar 

  50. Lechler E, Schramm W, Flosbach CW. The venous thrombotic risk in nonsurgical patients: epidemiological data and efficacy/safety profile of a low molecular weight heparin (enoxaparin). The PRIME Study Group. Haemostasis 1996; 26 Suppl. 2: 49–56

    PubMed  CAS  Google Scholar 

  51. Aventis Pharma Deutschland GmbH. Fachinformation zu Clexane ® 40 mg und Clexane® multidose 100 mg/ml. Bad Soden am Taunus: Aventis Pharma Deutschland GmbH, 2002 Dec

    Google Scholar 

  52. Samama MM, Gerotziafas GT. Comparative pharmacokinetics of LMWHs. Semin Thromb Hemost 2000; 26 Suppl. 1: 31–38

    Article  PubMed  CAS  Google Scholar 

  53. Statistisches Bundesarrt, editor. Gesundheitswesen. Fachserie 12, Reihe 6.3. Kostennachweisder Krankenhäuser 2001. Stuttgart: Metzler-Poeschel, 2003

  54. Gerste B, Schellschmidt H, Rosenow C. Personal im Krankenhaus: Entwicklungen 1991 bis 1999. In: Arnold M, Klauber J, Schellschmidt H, editors. Krankenhaus-Report 2001. Stuttgart: Schattauer, 2002: 13–46

    Google Scholar 

  55. Offermanns M. Krankenhaus Barometer — Herbstumfrage 2002. Düsseldorf: Deutsches Krankenhausinstitut e.V., 2003

    Google Scholar 

  56. Blum K. Entlastungspotenziale im Pflegedienst der Krankenhäuser. Das Krankenhaus 2003; 95: 459–462

    Google Scholar 

  57. Verordnung zum Fallpauschalensystem für Krankenhäuser (KFPV) vom 19. September 2002. BGBl, 2002: 3674-726

  58. Schädlich PK, Kentsch M, Weber M, et al. Economic evaluation of the MEDENOX (prophylaxis in MEDical patients with ENOXaparin) trial from the perspective of hospitals in Germany: results of a subgroup analysis [abstract no. PCV 39]. Value Health 2003; 6: 657

    Article  Google Scholar 

Download references

Acknowledgements

Funded by Sanofi-Aventis Deutschland GmbH, Berlin, Germany and Aventis Pharmaceuticals Inc., Bridgewater, NJ, USA, companies of the Sanofi-Aventis Group.

The authors would like to thank Sanofi-Aventis Deutschland and Aventis Pharmaceuticals USA, companies of the Sanofi-Aventis Group, for funding this study. J.G. Brecht and P.K. Schädlich are the principals of InForMed GmbH, the contractor of this study. W. Kämmerer, M. Kentsch and M. Weber, have received honoraria from InForMed GmbH. E. Huppertz, is a salaried employee of Sanofi-Aventis Deutschland, a company of the Sanofi-Aventis Group. V. Nadipelli was a salaried employee of Aventis Pharmaceuticals USA, a company of the Sanofi-Aventis Group, at the time this study was conducted and the article was written. However, the views expressed in this paper are solely those of the authors, who have no conflicts of interest directly relevant to the content of this study.

P.K. Schädlich is the main author. M. Kentsch and M. Weber provided information on treatment duration and resource consumption in natural units (survey in the medical clinics in Itzehoe and Cologne, respectively), revised the text, and checked for the accuracy of the medical aspects. W. Kämmerer provided prices of the consumed drugs, materials, disposables, and internal hospital prices of laboratory examinations (survey in the hospital pharmacy in Wiesbaden), revised the text and checked for the accuracy of the pharmaceutical aspects. J.G. Brecht, E. Huppertz and V. Nadipelli revised the text and checked for the accuracy of the health economic aspects. All authors revised and approved the manuscript.

The information contained in this article has been presented in part at the 6th Annual European Congress of the International Society for Pharmacoeconomics and Outcomes Research, Barcelona, Spain, November 2003; at the 110th Annual Congress of the German Society for Internal Medicine, Wiesbaden, Germany, April 2004; at the 2nd American College of Clinical Pharmacy and European Society of Clinical Pharmacy Joint Congress, Paris, France, April 2004; and is published in part in German exclusively with respect to the impact on the DRG-based reimbursement of German hospitals when using ENOX instead of LDUFH.[11]

Author information

Authors and Affiliations

  1. InForMed GmbH - Outcomes Research and Health Economics, Bureau Itzehoe, Conrad-Roentgen-Strasse 58 C, D-25524, Ingolstadt, Itzehoe, Germany

    Peter K. Schädlich & Josef Georg Brecht

  2. Medical Clinic, Clinics of Itzehoe, Itzehoe, Germany

    Michael Kentsch

  3. Medical Clinic I, Clinics of the City of Cologne, Cologne-Merheim, Germany

    Manfred Weber

  4. Hospital Pharmacy, Wiesbaden, Germany

    Wolfgang Kämmerer

  5. Berlex Laboratories, Wayne, New Jersey, USA

    Vijay Nadipelli

  6. Sanofi-Aventis Deutschland GmbH, Berlin, Germany

    Eduard Huppertz

Authors
  1. Peter K. Schädlich
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Michael Kentsch
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Manfred Weber
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Wolfgang Kämmerer
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Josef Georg Brecht
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Vijay Nadipelli
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Eduard Huppertz
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Peter K. Schädlich.

Electronic supplementary material

Rights and permissions

Reprints and permissions

About this article

Cite this article

Schädlich, P.K., Kentsch, M., Weber, M. et al. Cost Effectiveness of Enoxaparin as Prophylaxis against Venous Thromboembolic Complications in Acutely Ill Medical Inpatients. Pharmacoeconomics 24, 571–591 (2006). https://doi.org/10.2165/00019053-200624060-00005

Download citation

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.2165/00019053-200624060-00005

Keywords

Search

Navigation