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Pros and cons of new oral anticoagulants in the treatment of venous thromboembolism in patients with cancer

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Abstract

Patients with cancer account for 20 % of cases of venous thromboembolism (VTE). Cancer patients are at increased risk for VTE during the entire course of their disease, also in absence of traditional VTE risk factors. Furthermore, patients with VTE and cancer have an estimated risk of bleeding of 15–20 % per year while on anticoagulant treatment. For these reasons, treatment of acute VTE in patients with cancer remains a clinical challenge. In clinical studies, which included about 27,000 patients, new oral anticoagulants (NOACs) have been shown to be as effective and safe as conventional anticoagulation (heparin given with and followed by vitamin K antagonists) for the treatment of VTE. In these studies, 1227 patients with active cancer were enrolled. Preliminary results of subgroup analyses and meta-analyses of randomized clinical trials suggest that NOACs could represent an alternative to conventional anticoagulation in patients with active cancer. Further “ad hoc” studies evaluating the clinical benefit of treatment with NOACs in patients with VTE and cancer are needed.

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References

  1. Agnelli G, Verso M, Mandalà M, Gallus Cimminiello C et al (2014) A prospective study on survival in cancer patients with and without venous thromboembolism. Intern Emerg Med 9:559–567

    PubMed  Google Scholar 

  2. Lyman Gary H (2014) Impact of venous thromboembolism on survival in patients with advanced cancer: an unmet clinical need. Intern Emerg Med 9:497–499

    Article  PubMed  Google Scholar 

  3. Blom JW, Doggen CJ, Osanto S, Rosendaal FR (2005) Malignancies, prothrombotic mutations, and the risk of venous thrombosis. JAMA 293:715–722

    Article  CAS  PubMed  Google Scholar 

  4. Prandoni P, Lensing AW, Piccioli A, Bernardi E, Simioni P et al (2002) Recurrent venous thromboembolism and bleeding complications during anticoagulant treatment in patients with cancer and venous thrombosis. Blood 100:3484–3488

    Article  CAS  PubMed  Google Scholar 

  5. Heit JA, Silverstein MD, Mohr DN, Petterson TM, O’Fallon WM et al (2000) Risk factors for deep vein thrombosis and pulmonary embolism: a population-based case-control study. Arch Intern Med 160:809–815

    Article  CAS  PubMed  Google Scholar 

  6. Hutten BA, Prins MH, Gent M, Ginsberg J, Tijssen JG et al (2000) Incidence of recurrent thromboembolic and bleeding complications among patients with venous thromboembolism in relation to both malignancy and achieved international normalized ratio: a retrospective analysis. J Clin Oncol 18:3078–3083

    CAS  PubMed  Google Scholar 

  7. Heit JA, Mohr DN, Silverstein MD, Petterson TM, O’Fallon WM et al (2000) Predictors of recurrence after deep vein thrombosis and pulmonary embolism: a population- based cohort study. Arch Intern Med 160:761–768

    Article  CAS  PubMed  Google Scholar 

  8. Lee AY, Levine MN, Baker RI, Bowden C, Kakkar AK et al (2003) Low-molecular-weight heparin versus a coumarin for the prevention of recurrent venous thromboembolism in patients with cancer. N Engl J Med 349:146–153

    Article  CAS  PubMed  Google Scholar 

  9. Meyer G, Marjanovic Z, Valcke J, Lorcerie B, Gruel Y et al (2002) Comparison of low-molecular-weight heparin and warfarin for the secondary prevention of venous thromboembolism in patients with cancer: a randomized controlled study. Arch Intern Med 162:1729–1735

    Article  CAS  PubMed  Google Scholar 

  10. Hull RD, Pineo GF, Brant RF, Mah AF, Burke N et al (2006) Long-term low-molecular-weight heparin versus usual care in proximal-vein thrombosis patients with cancer. Am J Med 119:1062–1072

    Article  CAS  PubMed  Google Scholar 

  11. Deitcher SR, Kessler CM, Merli G, Rigas JR, Lyons RM et al (2006) Secondary prevention of venous thromboembolic events in patients with active cancer: enoxaparin alone versus initial enoxaparin followed by warfarin for a 180-day period. Clin Appl Thromb Hemost 12:389–396

    Article  CAS  PubMed  Google Scholar 

  12. Kearon C, Akl EA, Comerota AJ, Prandoni P, Bounameaux H et al (2012) Antithrombotic therapy for VTE disease: antithrombotic therapy and prevention of thrombosis, 9th ed: American College of Chest Physicians Evidence-Based Clinical Practice Guidelines. Chest 141:e419S–e494S

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  13. Chong LY, Fenu E, Stansby G, Hodgkinson S, Guideline Development G (2012) Management of venous thromboembolic diseases and the role of thrombophilia testing: summary of NICE guidance. BMJ 344:e3979

    Article  PubMed  Google Scholar 

  14. Baglin TP, Keeling DM, Watson HG, British Committee for Standards in H (2006) Guidelines on oral anticoagulation (warfarin): third edition—2005 update. Br J Haematol 132:277–285

    Article  CAS  PubMed  Google Scholar 

  15. Lyman GH, Bohlke K, Khorana AA, Kuderer NM, Lee AY et al (2015) Venous thromboembolism prophylaxis and treatment in patients with cancer: American Society of Clinical Oncology clinical practice guideline update 2014. J Clin Oncol 33:654–656

    Article  CAS  PubMed  Google Scholar 

  16. Barni M, Falanga A, Mandalà M et al (2013) Venous thromboembolism and cancer: guidelines of the Italian Association of Medical Oncology (AIOM) http://www.aiom.it/C_Common/Download.asp?file=/$Site$/Attivita_Scientifica/Linee_Guida/2013/Tromboembolismo_W9_27.09.2013.pdf

  17. Prandoni Paolo (2010) The treatment of venous thromboembolism in patients with cancer. Intern Emerg Med 5:27–30

    Article  Google Scholar 

  18. EINSTEIN investigators, Bauersachs R, Berkowitz SD, Brenner B, Buller HR, Decousus H et al (2010) Oral rivaroxaban for symptomatic venous thromboembolism. N Engl J Med 363:2499–2510

    Article  Google Scholar 

  19. Buller HR, Prins MH, Lensing AW, Decousus H, Jacobson BF et al (2012) Oral rivaroxaban for the treatment of symptomatic pulmonary embolism. N Engl J Med 366:1287–1297

    Article  PubMed  Google Scholar 

  20. Buller HR, Decousus H, Grosso MA, Mercuri M, Middeldorp S et al (2013) Edoxaban versus warfarin for the treatment of symptomatic venous thromboembolism. N Engl J Med 369:1406–1415

    Article  PubMed  Google Scholar 

  21. Schulman S, Kearon C, Kakkar AK, Mismetti P, Schellong S et al (2009) Dabigatran versus warfarin in the treatment of acute venous thromboembolism. N Engl J Med 361:2342–2352

    Article  CAS  PubMed  Google Scholar 

  22. Schulman S, Kakkar AK, Goldhaber SZ, Schellong S, Eriksson H et al (2014) Treatment of acute venous thromboembolism with dabigatran or warfarin and pooled analysis. Circulation 129:764–772

    Article  CAS  PubMed  Google Scholar 

  23. Agnelli G, Buller HR, Cohen A, Curto M, Gallus AS et al (2013) Oral apixaban for the treatment of acute venous thromboembolism. N Engl J Med 369:799–808

    Article  CAS  PubMed  Google Scholar 

  24. Loffredo L, Perri L, Del Ben M, Angelico F, Violi F (2014) New oral anticoagulants for the treatment of acute venous thromboembolism: are they safer than vitamin K antagonists? A meta-analysis of the interventional trials. Intern Emerg Med. doi:10.1007/s11739-014-1171-7

    Google Scholar 

  25. Akl EA, Labedi N, Barba M, Terrenato I, Sperati F et al (2011) Anticoagulation for the long-term treatment of venous thromboembolism in patients with cancer. Cochrane Database Syst Rev (6):CD006650. doi:10.1002/14651858.CD006650.pub3

  26. Vedovati MC, Germini F, Agnelli G, Becattini C (2015) Direct oral anticoagulants in patients with venous thromboembolism and cancer: a systematic review and meta-analysis. Chest 147:475–483

    Article  PubMed  Google Scholar 

  27. Van der Hulle T, den Exter PL, Kooiman J, van der Hoeven JJM, Huisman MV et al (2014) Meta-analysis of the efficacy and safety of new oral anticagulants in patients with cancer and venous thromboembolism. J Thormb Haemost 12:1116–1120

    Article  Google Scholar 

  28. Es Van, Coppens M, Schulman S, Middeldorp S, Buller HR (2014) Direct oral anticoagulants compared with vitamin K antagonists for acute venous thromboembolism: evidence from phase 3 trials. Blood 124:1968–1975

    Article  PubMed  Google Scholar 

  29. Prins MH, Lensing AW, Bauersachs R, van Bellen B, Bounameaux H et al (2013) Oral rivaroxaban versus standard therapy for the treatment of symptomatic venous thromboembolism: a pooled analysis of the EINSTEIN-DVT and PE randomized studies. Thromb J 11:21

    Article  PubMed Central  PubMed  Google Scholar 

  30. Schulman S, Eriksson H, Goldhaber SZ, Kakkar AJ, Kearon C et al (2013) Influence of active cancer on the efficacy and safety of dabigatran versus warfarin for the treatment of acute venous thromboembolism: a pooled analysis from RE-COVER and RE-COVER II ASH meeting abstract. Blood 122:582

    Google Scholar 

  31. Raskob GE, Buller HR, Angchaisuksiri P, Oh D, Boda Z et al (2013) Edoxaban for long-term treatment of venous thromboembolism in cancer patients: a sub-analysis from the Hokusai-VTE trial ASH meeting abstract. Blood 122:211

    Article  Google Scholar 

  32. Agnelli G, Buller HR, Cohen A, Curto M, Gallus AS et al (2014) Apixaban for the treatment of venous thromboembolism in cancer patients: data from the AMPLIFY trial. Eur Heart J 35:994

    Google Scholar 

  33. Kleinjan A, Aggarwal A, van der Geer A, Faselis C, Buller HR et al (2013) A worldwide survey to assess the current approach to the treatment of patients with cancer and venous thromboembolism. Thromb Haemost 110:959–965

    Article  CAS  PubMed  Google Scholar 

  34. Lee AY, Kampiusen PW, Meyer G, Bauersachs R, janas MS, jarner MF, Khorana A on behalf of the CATH Investigation (2014) A randomized trial of long-term tinzaparin, a low molecular weight heparin (LMWH), versus warfarin for treatment of acute venous thromboembolism (VTE) in cancer patients—the CATCH Study. Blood 124:LBA 2

  35. Monreal M, Falgà C, Valdès M, Suarez C, Gabriel F, Tolosa C, RIETE registry (2006) Fatal pulmonary embolism and fatal bleeding in cancer patients with venous thromboembolism. J Thomb Haemost 4:1950–1956

    Article  CAS  Google Scholar 

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Ethical standard

The Ethics Committee approved the study. This study has been performed in accordance with ethical standards laid down in the 1964 Declaration of Helsinki and its later amendments.

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Authors and Affiliations

  1. Medicina Interna e Cardiovascolare-Stroke Unit, Dipartimento di Medicina Interna, Università di Perugia, Via Gerardo Dottori, 06100, Perugia, Italy

    Melina Verso & Giancarlo Agnelli

  2. Department of Cardiothoracic and Vascular Sciences, University of Padua, Padua, Italy

    Paolo Prandoni

Authors
  1. Melina Verso
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  2. Giancarlo Agnelli
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  3. Paolo Prandoni
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Correspondence to Melina Verso.

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Verso, M., Agnelli, G. & Prandoni, P. Pros and cons of new oral anticoagulants in the treatment of venous thromboembolism in patients with cancer. Intern Emerg Med 10, 651–656 (2015). https://doi.org/10.1007/s11739-015-1233-5

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  • DOI: https://doi.org/10.1007/s11739-015-1233-5

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