Opinion statement
Cancer increases a patient’s risk for developing a venous thromboembolism (VTE) and is a relatively common finding in this population. Traditionally, anticoagulants used to treat VTE have included low molecular weight heparin (LMWH) or vitamin K antagonists (VKA). However, within the last several years, a newer class of anticoagulant, the direct oral anticoagulants (DOACs), has emerged as a potential option for pharmacologic thromboprophylaxis and for treatment of VTE in patients with cancer. While data is still limited and evolving, DOACs offer several benefits that are worth considering, including ease of administration and similar efficacy compared to LMWH in preventing recurrent VTE. However, some studies have reported a notable risk of increased bleeding associated with the use of DOACs. Additional studies are underway to evaluate the role of DOACs compared to LMWH in the setting of cancer. In our practice, based on existing data, we have been using DOACs for the chronic treatment of acute VTE and prevention of recurrent VTE in patients who do not have contraindications to anticoagulation and do not have severe renal insufficiency (creatinine clearance < 30 mL/min). For cancer patients admitted to the hospital with an acute medical illness, we use LMWH for primary prevention of VTE. In the perioperative setting, for patients undergoing major surgery with an active cancer, we prefer pharmacologic thromboprophylaxis with LMWH, although there is some emerging evidence that DOACs may be safe in this setting.
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Bellesoeur A, Thomas-Schoemann A, Allard M, et al. Pharmacokinetic variability of anticoagulants in patients with cancer-associated thrombosis: clinical consequences. Crit Rev Oncol Hematol. 2018;129:102–12.
Cohen A, Maraveyas A, Beyer-Westendorf J, et al. COSIMO – patients with active cancer changing to rivaroxaban for the treatment and prevention of recurrent venous thromboembolism: a non-interventional study. Thromb J. 2018;16:21 1–9.
Imberti D, Benedetti R. Primary prophylaxis of VTE in cancer outpatients. Thrombosis Research. 2016;140S1:S103–8.
Wun T, White R. Epidemiology of cancer-related venous thromboembolism. Best Pract Res Clin Haematol. 2010;22:9–23.
Streiff M, Holmstrom B, Angelini D, et al. Cancer-associated venous thromboembolic disease. In: NCCN Clinical Practice Guidelines in Oncology. National Comprehensive Cancer Network. 2019. https://www.nccn.org/professionals/physician_gls/pdf/vte.pdf. Accessed 10 June 2019.
Lyman G, Bohlke K, Khorana A, et al. Venous thromboembolism prophylaxis and treatment in patients with cancer: American society of clinical oncology clinical practice guideline update 2014. J Clin Oncol. 2015;33:654–6.
Wang T, Li A, Garcia D. Managing thrombosis in cancer patients. Res Prac Thromb Haemost. 2018;2:429–38.
Daniels P. Peri-procedural management of patients taking oral anticoagulants. BMJ. 2015;351:h2391.
van Es N, Coppens M, Schulman S, et al. Direct oral anticoagulants compared with vitamin K antgonists for acute venous thromboembolism: evidence from phase 3 trials. Blood. 2014;124:1968–75.
Khorana A, Kuderer N, Culakova E, Lyman G, Francis C. Development and validation of a predictive model for chemotherapy-associated thrombosis. Blood. 2008;111:4902–7.
Agnelli G, Gussoni G, Bianchini C, Verso M, Mandala M, Cavanna L, 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. 2009;10:943–9.
Agnelli G, George D, Kakkar A, et al. Semuloparin for thromboprophylaxis in patients receiving chemotherapy for cancer. N Engl J Med. 2012;366:601–9.
• Carrier M, Abou-Nassar K, Mallick R, et al. Apixaban to prevent venous thromboembolism in patients with cancer. N Engl J Med. 2019;380:711–9 Established efficacy and safety of apixaban for primary prevention of VTE in ambulatory patients with cancer who are at intermediate-to-high risk of VTE.
• Khorana A, Soff G, Kakkar A, et al. Rivaroxaban for thromboprophylaxis in high-risk ambulatory patients with cancer. N Engl J Med. 2019;380:720–8 Established efficacy and safety of rivaroxaban for primary prevention of VTE in ambulatory patients with cancer who are at intermediate-to-high risk of VTE.
Agnelli G. Direct oral anticoagulants for thromboprophylaxis in ambulatory patients with cancer. N Engl J Med. 2019;380:781–3.
Cohen A, Spiro T, Büller H, et al. Rivaroxaban for thromboprophylaxis in acutely ill medical patients. N Engl J Med. 2013;368:513–23.
Goldhaber S, Leizorovicz A, Kakkar A, et al. Apixaban versus enoxaparin for thromboprophylaxis in medically ill patients. N Engl J Med. 2011;365:2167–77.
Caprini J. Thrombosis risk assessment as a guide to quality patient care. Dis Mon. 2005;51:70–8.
Di Nisio M, Porreca E, Otten HM, et al. Primary prophylaxis for venous thromboembolism in ambulatory cancer patients receiving chemotherapy. Cochrane Database Syst Rev. 2014;12:CD008500.
Schmeler K, Langley G, Cain K, et al. Venous thromboembolism (VTE) rates following the implementation of extended duration prophylaxis for patients undergoing surgery for gynecologic malignancies. Gynecol Oncol. 2013;128:1–13.
•• Felder S, Rasmussen M, King R, et al. Prolonged thromboprophylaxis with low molecular weight heparin for abdominal or pelvic surgery. Cochrane Database of Systemic Reviews. 2019. Extended thromboprophylaxis with LMWH significantly decreased the risk of VTE compared to short-duration thromboprophylaxis in patients undergoing abdominal or pelvic surgery.
Marques de Marino P, Horcajo R, Grandal G, et al. Thromboprophylaxis in gynecologic cancer surgery: is extened prophylaxis with low molecular weight heparin justified. Eur J Obstet Gynecol Reprod Biol. 2018;230:90–5.
Beyer-Westendorf J, Mouret P, Turpie A. Rivaroxaban for venous thromboembolism prevention after major orthopedic surgery: translating trial data into routine clinical practice. Orthop Res Rev. 2017;9:1–11.
Guntapalli S, Brennecke A, Sheeder J, et al. A multiinstitutional, prospective randomized open-blinded end-point trial for safety of oral apixaban versus subcutaneous enoxaparin for thromboprophylaxis in women with suspected gynecologic malignancy. Gynecol Oncol. 2017;145:221.
Guntupalli S, Brennecke A, Babayan Lisa L, et al. 15 oral apixaban compared to subcutaneous enoxaparin for thromboprophylaxis in women undergoing surgery for suspected gynecologic cancer: final results of a multi-institutional randomized, controlled trial. Int J Gynecol Cancer. 2019;29:A9.
Lee A, Levine M, Baker R, 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;349:145–53.
Xing J, Yin X, Chen D. Rivaroxaban versus enoxaparin for the prevention of recurrent venous thromboembolism in patients with cancer: a meta-analysis. Medicine. 2018;97:1–4.
Djulbegovic M, Lee A. An update on the “Novel” and direct oral anticoagulants, and long-term anticoagulant therapy. Clin Chest Med. 2018;39:583–593.29.
Shah S, Norby F, Datta Y, et al. Comparative effectiveness of direct oral anticoagulants and warfarin in patients with cancer and atrial fibrillation. Blood Advances. 2018;2:200–9.
Lee A, Kamphuisen P, Meyer G, et al. Tinzaparin vs warfarin for treatment of acute thromboembolism in patients with active cancer: a randomized clinical trial. J Am Med Assoc. 2015;314:677–86.
Francis C, Kessler C, Goldhaber S, et al. Treatment of venous thromboembolism in cancer patients with dalteparin for up to 12 months: the DALTECAN study. J Thromb Haemost. 2015;13:1028–35.
Hull R, Pineo G, Brant R, et al. Long-term low-molecular-weight heparin versus usual care in proximal-vein thrombosis patients with cancer. Am J Med. 2006;119:1062–72.
Meyer G, Marjanovic Z, Valcke J, et al. 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. 2002;162:1729–35.
Raskob G, van Es N, Verhamme P, et al. Edoxaban for the treatment of cancer-associated venous thromboembolism. N Engl J Med. 2018;378:615–24.
Mantha S, Laube E, Miao Y, et al. Safe and effective use of rivaroxaban for treatment of cancer-associated venous thromboembolic disease: a prospective cohort study. J Thromb Thrombolysis. 2017;43:166–71.
Prins M, Lensing A, Brighton T, et al. Oral rivaroxaban versus enoxaparin with vitamin K antagonist for the treatment of symptomatic venous thromboembolism in patients with cancer (EINSTEIN-DVT and EINSTEIN-PE): a pooled subgroup analysis of two randomized controlled trials. Lancet Haematol. 2014;1:e37–46.
Young A, Marshall A, Thirlwall J, et al. Comparison of an oral factor Xa inhibitor with low molecular weight heparin in patients with cancer with venous thromboembolism: results of a randomized trial (SELTECT-D). J Clin Oncol. 2018;36:2017–23.
Bauersachs R, Berkowitz S, Brenner B, et al. Oral rivaroxaban for symptomatic venous thromboembolism. N Engl J Med. 2010;363:2499–510.
Posch F, Königsbrügge O, Zielinksi C, et al. Treatment of venous thromboembolism in patients with cancer: a network meta-analysis comparing efficacy and safety of anticoagulants. Thromb Res. 2015;136:582–9.
Sobieraj D, Baker W, Smith E, et al. Anticoagulation for the treatment of cancer-associated thrombosis: a systemic review and network meta-analysis of randomized trials. Clin Appl Thromb Hemost. 2018;24:182S–7S.
•• Li A, Garcia D, Lyman G, et al. Direct oral anticoagulant (DOAC) versus low-molecular weight heparin (LMWH) for treatment of cancer associated thrombosis (CAT): a systemic review and meta-analysis. Thromb Res. 2018;173:158–63 1–6. Demonstrated efficacy DOACs compared to LMWH in prevention of recurrent VTE at 6 months.
Vedovati M, Giustozzi M, Bonitta G, et al. Efficacy and safety of anticoagulant agents in patients with venous thromboembolism and cancer: a network meta-analysis. Thromb Res. 2018;170:175–80.
Riess H, Prandoni P, Harder S, Kreher S, Bauersachs R. Direct oral anticoagulants for the treatment of venous thromboembolism in cancer patients: potential for drug-drug interactions. Crit Rev Oncol. 2018;132:169–79.
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Tulsi Patel declares that she has no conflict of interest.
David A. Iglesias declares that he has no conflict of interest.
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Patel, T., Iglesias, D.A. Venous Thromboembolism Treatment and Prevention in Cancer Patients: Can We Use Pills Yet?. Curr. Treat. Options in Oncol. 21, 43 (2020). https://doi.org/10.1007/s11864-020-00744-w
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DOI: https://doi.org/10.1007/s11864-020-00744-w