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

Allyson M. Pishko; Kenneth J. Smith; Margaret V. Ragni

doi:10.1160/TH12-03-0185

Thrombosis and Haemostasis, Table of Contents

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

¹Department of Medicine, Division Hematology/Oncology, University of Pittsburgh, Pittsburgh, Pennsylvania, USA

,

Kenneth J. Smith

²Section 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

¹Department of Medicine, Division Hematology/Oncology, University of Pittsburgh, Pittsburgh, Pennsylvania, USA

³Hemophilia Center of Western PA, Pittsburgh, Pennsylvania, USA

› Author Affiliations

Abstract

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

Full Text

References

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.
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.
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.
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.
5 Browder T, Folkman J, Pirie-Shepherd S. The hemostatic system as a regulator of angiogenesis. J Biol Chem 2000; 275: 1521-1524.
6 Rickles FR, Patierno S, Fernandez PM. Tissue factor, thrombin, and cancer. Chest 2003; 124: 58S-68S.
7 Zacharski LR, Ornstein DL. Heparin and cancer. Thromb Haemost 1998; 80: 10-23.
8 Zacharski LR, Ornstein DL, Mamourian AC. Low-molecular-weight heparin and cancer. Semin Thromb Hemost 2000; 26 Suppl 1 69-77.
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.
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.
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.
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.
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.
14 Kahn SR, Lim W, Dunn AS. et al. Prevention of VTE in nonsurgical patients: antithrombotic therapy and prevention of thrombosis, 9^th ed: American College of Chest Physicians evidence-based clinical practice guidelines. Chest 2012; 14 (Suppl) e195S-226S.
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.
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.
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.
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.
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.
20 Aujesky D, Smith KJ, Robert MS. Oral anticoagulation strategies after a first idiopathic venous thromboembolic event. Am J Med 2005; 118: 625-635.
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.
22 Prandoni P, Flanaga A, Piccioli A. Cancer and venous thromboembolism. Lancet Oncol 2005; 06: 401-410.
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.
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.
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.
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.
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.