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Published in: Current Treatment Options in Oncology 5/2020

01-05-2020 | Direct Oral Anticoagulant | Gynecologic Cancers (LA Cantrell, Section Editor)

Venous Thromboembolism Treatment and Prevention in Cancer Patients: Can We Use Pills Yet?

Authors: Tulsi Patel, MD, David A. Iglesias, MD, MS

Published in: Current Treatment Options in Oncology | Issue 5/2020

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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.
Literature
1.
go back to reference 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.CrossRef 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.CrossRef
2.
go back to reference 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. 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.
3.
go back to reference Imberti D, Benedetti R. Primary prophylaxis of VTE in cancer outpatients. Thrombosis Research. 2016;140S1:S103–8.CrossRef Imberti D, Benedetti R. Primary prophylaxis of VTE in cancer outpatients. Thrombosis Research. 2016;140S1:S103–8.CrossRef
4.
go back to reference Wun T, White R. Epidemiology of cancer-related venous thromboembolism. Best Pract Res Clin Haematol. 2010;22:9–23.CrossRef Wun T, White R. Epidemiology of cancer-related venous thromboembolism. Best Pract Res Clin Haematol. 2010;22:9–23.CrossRef
6.
go back to reference 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.CrossRef 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.CrossRef
7.
go back to reference Wang T, Li A, Garcia D. Managing thrombosis in cancer patients. Res Prac Thromb Haemost. 2018;2:429–38.CrossRef Wang T, Li A, Garcia D. Managing thrombosis in cancer patients. Res Prac Thromb Haemost. 2018;2:429–38.CrossRef
8.
go back to reference Daniels P. Peri-procedural management of patients taking oral anticoagulants. BMJ. 2015;351:h2391.CrossRef Daniels P. Peri-procedural management of patients taking oral anticoagulants. BMJ. 2015;351:h2391.CrossRef
9.
go back to reference 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.PubMed 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.PubMed
10.
go back to reference 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.CrossRef 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.CrossRef
11.
go back to reference 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.CrossRef 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.CrossRef
12.
go back to reference 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.CrossRef 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.CrossRef
13.
go back to reference • 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.CrossRef • 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.CrossRef
14.
go back to reference • 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.CrossRef • 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.CrossRef
15.
go back to reference Agnelli G. Direct oral anticoagulants for thromboprophylaxis in ambulatory patients with cancer. N Engl J Med. 2019;380:781–3.CrossRef Agnelli G. Direct oral anticoagulants for thromboprophylaxis in ambulatory patients with cancer. N Engl J Med. 2019;380:781–3.CrossRef
16.
go back to reference Cohen A, Spiro T, Büller H, et al. Rivaroxaban for thromboprophylaxis in acutely ill medical patients. N Engl J Med. 2013;368:513–23.CrossRef Cohen A, Spiro T, Büller H, et al. Rivaroxaban for thromboprophylaxis in acutely ill medical patients. N Engl J Med. 2013;368:513–23.CrossRef
17.
go back to reference 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.CrossRef 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.CrossRef
18.
go back to reference Caprini J. Thrombosis risk assessment as a guide to quality patient care. Dis Mon. 2005;51:70–8.CrossRef Caprini J. Thrombosis risk assessment as a guide to quality patient care. Dis Mon. 2005;51:70–8.CrossRef
19.
go back to reference 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. 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.
20.
go back to reference 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.CrossRef 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.CrossRef
21.
go back to reference •• 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. •• 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.
22.
go back to reference 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.CrossRef 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.CrossRef
23.
go back to reference 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.PubMedPubMedCentral 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.PubMedPubMedCentral
24.
go back to reference 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.CrossRef 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.CrossRef
25.
go back to reference 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. 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.
26.
go back to reference 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. 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.
27.
go back to reference 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.CrossRef 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.CrossRef
28.
go back to reference 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.CrossRef 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.CrossRef
29.
go back to reference 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.CrossRef 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.CrossRef
30.
go back to reference 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.CrossRef 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.CrossRef
31.
go back to reference 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.CrossRef 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.CrossRef
32.
go back to reference 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.CrossRef 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.CrossRef
33.
go back to reference 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.CrossRef 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.CrossRef
34.
go back to reference 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.CrossRef 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.CrossRef
35.
go back to reference 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.CrossRef 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.CrossRef
36.
go back to reference 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.CrossRef 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.CrossRef
37.
go back to reference 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.CrossRef 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.CrossRef
38.
go back to reference Bauersachs R, Berkowitz S, Brenner B, et al. Oral rivaroxaban for symptomatic venous thromboembolism. N Engl J Med. 2010;363:2499–510.CrossRef Bauersachs R, Berkowitz S, Brenner B, et al. Oral rivaroxaban for symptomatic venous thromboembolism. N Engl J Med. 2010;363:2499–510.CrossRef
39.
go back to reference 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.CrossRef 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.CrossRef
40.
go back to reference 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.CrossRef 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.CrossRef
41.
go back to reference •• 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.CrossRef •• 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.CrossRef
42.
go back to reference 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.CrossRef 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.CrossRef
43.
go back to reference 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.CrossRef 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.CrossRef
Metadata
Title
Venous Thromboembolism Treatment and Prevention in Cancer Patients: Can We Use Pills Yet?
Authors
Tulsi Patel, MD
David A. Iglesias, MD, MS
Publication date
01-05-2020
Publisher
Springer US
Published in
Current Treatment Options in Oncology / Issue 5/2020
Print ISSN: 1527-2729
Electronic ISSN: 1534-6277
DOI
https://doi.org/10.1007/s11864-020-00744-w

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