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Thromb Haemost 2012; 108(02): 303-310
DOI: 10.1160/TH12-03-0185
Blood Coagulation, Fibrinolysis and Cellular Haemostasis
Schattauer GmbH

Anticoagulation in ambulatory cancer patients with no indication for prophylactic or therapeutic anticoagulation

A cost-effectiveness analysis from a U.S. perspective
Allyson M. Pishko
1   Department of Medicine, Division Hematology/Oncology, University of Pittsburgh, Pittsburgh, Pennsylvania, USA
,
Kenneth J. Smith
2   Section of Decision Sciences and Clinical Systems Modeling, Division Internal Medicine and Center for Research on Health Care Data Center, Pittsburgh, Pennsylvania, USA
,
Margaret V. Ragni
1   Department of Medicine, Division Hematology/Oncology, University of Pittsburgh, Pittsburgh, Pennsylvania, USA
3   Hemophilia Center of Western PA, Pittsburgh, Pennsylvania, USA
› Author Affiliations Financial support: The study was supported by HHS Federal Region III Hemophilia Treatment Centers, Grant #1-H-30-MC-0038–01; the Centers for Diseases Control Prevention of Complications of Hemophilia Grant U10DD000193; and the Pennsylvania Department of Health State SAP #04100000330.
Further Information

Publication History

Received: 22 March 2012

Accepted after major revision: 27 April 2012

Publication Date:
25 November 2017 (online)

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Summary

Venous thromboembolism (VTE) occurs frequently in cancer patients and is a major cause of mortality. Although anticoagulation (AC) may have anti-tumour effects, it is recommended in cancer patients only for indications unrelated to these effects. A Markov model was constructed to estimate when prophylactic AC, given during four months of chemotherapy following a new cancer diagnosis, would be economically reasonable in ambulatory cancer patients with no VTE history. Risks and costs of major and minor bleeding, VTE, and death were obtained from the literature, including a 2011 Cochrane review of AC in cancer inpatients with no conventional indication. In the model, AC was low-molecular-weight-heparin (LMWH), and effects were modeled over a 24-month period. Model outputs were quality-adjusted life years (QALY) and the incremental cost-effectiveness ratio (ICER). In the base case analysis, when prophylactic AC had a two-year relative mortality risk of 0.92, there was a gain of 0.0354 QALY, for an ICER of $90,893/QALY gained, compared with no AC. In sensitivity analyses, AC prophylaxis cost less than $100,000/QALY, if two-year mortality exceeded 75%, or if AC costs were less than $1,076 per month, or if LMWH relative mortality risk was less than 0.927. Results were not sensitive to variation in VTE relative risk on AC, nor to major or minor bleeding risk on AC. A probabilistic sensitivity analysis also favoured prophylactic AC. In conclusion, prophylactic LMWH given to decrease cancer-related mortality, with no conventional indication, appears economically reasonable if its suggested mortality benefit is confirmed in future trials.

Keywords

Anticoagulation - cancer - low-molecular-weight heparin - venous thromboembolism
 

  • References

  • 1 Khorana AA, Francis CW, Culakova E. et al. Thromboembolism is a leading cause of death in cancer patients receiving outpatient chemotherapy. J Thromb Haemost 2007; 05: 632-634.
    CrossrefPubMedGoogle Scholar
  • 2 Ay C, Simanek R, Vormittag R. et al. High plasma levels of soluble P-selectin are predictive of venous thromboembolism in cancer patients: results from the Vienna cancer and thrombosis study (CATS). Blood 2008; 112: 2703-2708.
    CrossrefPubMedGoogle Scholar
  • 3 Ay C, Vormittag R, Dunkler D. et al. D-dimer and prothrombin fragment 1+2 predict venous thromboembolism in patients with cancer: results from the Vienna cancer and thrombosis study. J Clin Oncol 2009; 27: 4124-4129.
    CrossrefPubMedGoogle Scholar
  • 4 Kuderer NM, Ortel TL, Francis CW. Impact of venous thromboembolism and anti-coagulation on cancer and cancer survival. J Clin Oncol 2009; 27: 4902-4911.
    CrossrefPubMedGoogle Scholar
  • 5 Browder T, Folkman J, Pirie-Shepherd S. The hemostatic system as a regulator of angiogenesis. J Biol Chem 2000; 275: 1521-1524.
    CrossrefPubMedGoogle Scholar
  • 6 Rickles FR, Patierno S, Fernandez PM. Tissue factor, thrombin, and cancer. Chest 2003; 124: 58S-68S.
    CrossrefPubMedGoogle Scholar
  • 7 Zacharski LR, Ornstein DL. Heparin and cancer. Thromb Haemost 1998; 80: 10-23.
    Article in Thieme ConnectPubMedGoogle Scholar
  • 8 Zacharski LR, Ornstein DL, Mamourian AC. Low-molecular-weight heparin and cancer. Semin Thromb Hemost 2000; 26 Suppl 1 69-77.
    Article in Thieme ConnectPubMedGoogle Scholar
  • 9 Lyman GH, Khorana AA, Falanga A. et al. American Society of Clinical Oncology Guideline: Recommendations for venous thromboembolism prophylaxis and treatment in patients with cancer. J Clin Oncol 2007; 25: 5490-5505.
    CrossrefPubMedGoogle Scholar
  • 10 Kuderer NM, Khorana AA, Lyman GH. et al. A meta-analysis and systemic review of the efficacy and safety of anticoagulants as cancer treatment: impact on survival and bleeding complications. Cancer 2007; 110: 1149-1161.
    CrossrefPubMedGoogle Scholar
  • 11 Lazo-Langner A, Goss GD, Spaans JN. et al. The effect of low-molecular-weight heparin on cancer survival. A systematic review and meta-analysis of randomized trials. J Thromb Haemost 2007; 05: 729-737.
    PubMedGoogle Scholar
  • 12 Akl EA, Doormaal FF, Barba M. et al. Parenteral anticoagulation may prolong the survival or patients with limited small cell lung cancer: a Cochrane systematic review. J Exp Clin Cancer Res 2008; 27: 1-10.
    CrossrefPubMedGoogle Scholar
  • 13 AklEA Vasireddi SR, Gunukula S. et al. Anticoagulation for the initial treatment of venous thromboembolism in patients with cancer. Cochrane Database Syst Rev 2011; 06 CD006649 1-59.
    PubMedGoogle Scholar
  • 14 Kahn SR, Lim W, Dunn AS. et al. Prevention of VTE in nonsurgical patients: antithrombotic therapy and prevention of thrombosis, 9th ed: American College of Chest Physicians evidence-based clinical practice guidelines. Chest 2012; 14 (Suppl) e195S-226S.
    CrossrefPubMedGoogle Scholar
  • 15 Khorana AA, Streiff MB, Farge D. et al. Venous thromboembolism prophylaxis and treatment in cancer: a consensus statement of major guideline panels and call to action. J Clin Oncol 2009; 27: 4919-4926.
    CrossrefPubMedGoogle Scholar
  • 16 Agnelli G, Gussoni G, Bianchini C. et al. Nadroparin for the prevention of thromboembolic events in ambulatory patients with metastatic or locally advanced solid cancer receiving chemotherapy: a randomized, placebo-controlled, double-blind study. Lancet Oncol 2011; 10: 943-949.
    PubMedGoogle Scholar
  • 17 AklEA Gunukula S, Barba M. et al. Parenteral anticoagulation in patients with cancer who have no therapeutic or prophylactic indication for anticoagulation. Cochrane Database Syst Rev 2011; 04 CD006652 1-50.
    PubMedGoogle Scholar
  • 18 Agnelli G, George JG, Kakkar AK. et al. Semuloparin for thromboprophylaxis in patients receiving chemotherapy for cancer. N Engl J Med 2012; 366: 601-609.
    CrossrefPubMedGoogle Scholar
  • 19 AklEA Vasireddi SR, Gunukula S. et al. Oral anticoagulation in patients with cancer who have no therapeutic or prophylactic indication for anticoagulation. Cochrane Database Syst Rev 2011; 06 CD006466 1-39.
    PubMedGoogle Scholar
  • 20 Aujesky D, Smith KJ, Robert MS. Oral anticoagulation strategies after a first idiopathic venous thromboembolic event. Am J Med 2005; 118: 625-635.
    CrossrefPubMedGoogle Scholar
  • 21 Aujesky D, Smith KJ, Cornuz J. et al. Cost-effectiveness of low-molecular weight heparin for secondary prophylaxis of cancer-related venous thromboembolism. Thromb Haemost 2005; 93: 592-599.
    Article in Thieme ConnectPubMedGoogle Scholar
  • 22 Prandoni P, Flanaga A, Piccioli A. Cancer and venous thromboembolism. Lancet Oncol 2005; 06: 401-410.
    CrossrefPubMedGoogle Scholar
  • 23 Lee AYY, Levine MN, Baker RI. et al. Low-molecular-weight heparin versus a coumarin for the prevention of recurrent venous thromboembolism in patients with cancer. N Engl J Med 2003; 349: 146-153.
    CrossrefPubMedGoogle Scholar
  • 24 Aujesky D, Smith KJ, Cornuz J. et al. Cost-effectiveness of low-molecular-weight heparin for treatment of pulmonary embolism. Chest 2005; 128: 1601-1610.
    CrossrefPubMedGoogle Scholar
  • 25 Red Book: Pharmacy’s Fundamental Reference. Thomson Health Care; Montvale NJ: 2010
  • 26 Healthcare Cost and Utilization Project (HCUP). 2009 Agency for Healthcare Research and Quality (AHRQ). Available at: http://hcupnet.ahrq.gov Accessed January 31, 2012.
    PubMedGoogle Scholar
  • 27 Braithwaite RS, Meltzer DO, King Jr JT. et al. What does the value of modern medicine say about the $50,000 per quality-adjusted life-year decision rule?. Med Care 2008; 46: 349-356.
    CrossrefPubMedGoogle Scholar
  • 28 Ageno W, Squizzato A, Ambrosini F. et al. Thrombosis prophylaxis in medical patients: a retrospective review of clinical practice patterns. Haematologica 2002; 87: 746-750.
    PubMedGoogle Scholar