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Published in: Supportive Care in Cancer 3/2018

01-03-2018 | Review Article

The role of direct oral anticoagulants in cancer-related venous thromboembolism: a perspective beyond the guidelines

Author: Cristhiam M. Rojas-Hernandez

Published in: Supportive Care in Cancer | Issue 3/2018

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Abstract

Cancer-related venous thromboembolism (Wickham et al., Intern Med J 42(6):698–708, 2012) is an important source of morbidity and mortality in that population. The standard of care for the treatment of cancer-related venous thromboembolism (VTE) is a low molecular weight heparin (LMWH) for long periods of time. The favorable clinical trial results for efficacy and safety and availability of direct oral anticoagulants (DOAC) have remodeled the care and options for treatment of venous thromboembolism in the adult population. The data of cancer population-subgroup analysis of those studies have shown that DOAC are as effective and safe as conventional long-term oral anticoagulation with vitamin K antagonists (VKA). Additionally, non-controlled retrospective and prospective cohort data have been published describing efficacy and safety outcomes for the use of DOAC in cancer-related VTE. Altogether, the results from clinical studies have shown that direct oral anticoagulants may represent a treatment option for cancer-related VTE and an alternative to anticoagulation with VKA. Little is known about the patient-centered and system-based variables that determine the use of DOAC outside consensus guidelines, neither is known the impact of different anticoagulant modalities in adherence and quality of life in cancer patients. The objectives of this manuscript are to summarize the clinical trial-based and cohort data of cancer patients treated with DOAC for VTE and to highlight the aspects that may influence adherent to therapy, effectiveness, and safety outcomes in the treatment of cancer-related VTE.
Literature
3.
go back to reference YB Y, Gau JP, Liu CY, Yang MH, Chiang SC, Hsu HC, Hong YC, Hsiao LT, Liu JH, Chiou TJ, Chen PM, Lee TS, Chou LF, Tzeng CH, Chen TJ (2012) A nation-wide analysis of venous thromboembolism in 497,180 cancer patients with the development and validation of a risk-stratification scoring system. Thromb Haemost 108(2):225–235. https://doi.org/10.1160/TH12-01-0010 CrossRef YB Y, Gau JP, Liu CY, Yang MH, Chiang SC, Hsu HC, Hong YC, Hsiao LT, Liu JH, Chiou TJ, Chen PM, Lee TS, Chou LF, Tzeng CH, Chen TJ (2012) A nation-wide analysis of venous thromboembolism in 497,180 cancer patients with the development and validation of a risk-stratification scoring system. Thromb Haemost 108(2):225–235. https://​doi.​org/​10.​1160/​TH12-01-0010 CrossRef
5.
go back to reference Lyman GH, Khorana AA, Kuderer NM, Lee AY, Arcelus JI, Balaban EP, Clarke JM, Flowers CR, Francis CW, Gates LE, Kakkar AK, Key NS, Levine MN, Liebman HA, Tempero MA, Wong SL, Prestrud AA, Falanga A, American Society of Clinical Oncology Clinical P (2013) Venous thromboembolism prophylaxis and treatment in patients with cancer: American Society of Clinical Oncology clinical practice guideline update. J Clin Oncol 31(17):2189–2204. https://doi.org/10.1200/JCO.2013.49.1118 CrossRefPubMed Lyman GH, Khorana AA, Kuderer NM, Lee AY, Arcelus JI, Balaban EP, Clarke JM, Flowers CR, Francis CW, Gates LE, Kakkar AK, Key NS, Levine MN, Liebman HA, Tempero MA, Wong SL, Prestrud AA, Falanga A, American Society of Clinical Oncology Clinical P (2013) Venous thromboembolism prophylaxis and treatment in patients with cancer: American Society of Clinical Oncology clinical practice guideline update. J Clin Oncol 31(17):2189–2204. https://​doi.​org/​10.​1200/​JCO.​2013.​49.​1118 CrossRefPubMed
6.
go back to reference Prandoni P, Lensing AW, Piccioli A, Bernardi E, Simioni P, Girolami B, Marchiori A, Sabbion P, Prins MH, Noventa F, Girolami A (2002) Recurrent venous thromboembolism and bleeding complications during anticoagulant treatment in patients with cancer and venous thrombosis. Blood 100(10):3484–3488. https://doi.org/10.1182/blood-2002-01-0108 CrossRefPubMed Prandoni P, Lensing AW, Piccioli A, Bernardi E, Simioni P, Girolami B, Marchiori A, Sabbion P, Prins MH, Noventa F, Girolami A (2002) Recurrent venous thromboembolism and bleeding complications during anticoagulant treatment in patients with cancer and venous thrombosis. Blood 100(10):3484–3488. https://​doi.​org/​10.​1182/​blood-2002-01-0108 CrossRefPubMed
7.
go back to reference Farge D, Debourdeau P, Beckers M, Baglin C, Bauersachs RM, Brenner B, Brilhante D, Falanga A, Gerotzafias GT, Haim N, Kakkar AK, Khorana AA, Lecumberri R, Mandala M, Marty M, Monreal M, Mousa SA, Noble S, Pabinger I, Prandoni P, Prins MH, Qari MH, Streiff MB, Syrigos K, Bounameaux H, Buller HR (2013) International clinical practice guidelines for the treatment and prophylaxis of venous thromboembolism in patients with cancer. J Thrombosis Haemostasis: JTH 11(1):56–70. https://doi.org/10.1111/jth.12070 CrossRef Farge D, Debourdeau P, Beckers M, Baglin C, Bauersachs RM, Brenner B, Brilhante D, Falanga A, Gerotzafias GT, Haim N, Kakkar AK, Khorana AA, Lecumberri R, Mandala M, Marty M, Monreal M, Mousa SA, Noble S, Pabinger I, Prandoni P, Prins MH, Qari MH, Streiff MB, Syrigos K, Bounameaux H, Buller HR (2013) International clinical practice guidelines for the treatment and prophylaxis of venous thromboembolism in patients with cancer. J Thrombosis Haemostasis: JTH 11(1):56–70. https://​doi.​org/​10.​1111/​jth.​12070 CrossRef
14.
go back to reference Agnelli G, Buller HR, Cohen A, Gallus AS, Lee TC, Pak R, Raskob GE, Weitz JI, Yamabe T (2015) Oral apixaban for the treatment of venous thromboembolism in cancer patients: results from the AMPLIFY trial. J Thrombosis Haemostasis: JTH 13(12):2187–2191. https://doi.org/10.1111/jth.13153 CrossRef Agnelli G, Buller HR, Cohen A, Gallus AS, Lee TC, Pak R, Raskob GE, Weitz JI, Yamabe T (2015) Oral apixaban for the treatment of venous thromboembolism in cancer patients: results from the AMPLIFY trial. J Thrombosis Haemostasis: JTH 13(12):2187–2191. https://​doi.​org/​10.​1111/​jth.​13153 CrossRef
15.
go back to reference Prins MH, Lensing AW, Brighton TA, Lyons RM, Rehm J, Trajanovic M, Davidson BL, Beyer-Westendorf J, Pap AF, Berkowitz SD, Cohen AT, Kovacs MJ, Wells PS, Prandoni P (2014) 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 randomised controlled trials. Lancet Haematol 1(1):e37–e46. https://doi.org/10.1016/S2352-3026(14)70018-3 CrossRefPubMed Prins MH, Lensing AW, Brighton TA, Lyons RM, Rehm J, Trajanovic M, Davidson BL, Beyer-Westendorf J, Pap AF, Berkowitz SD, Cohen AT, Kovacs MJ, Wells PS, Prandoni P (2014) 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 randomised controlled trials. Lancet Haematol 1(1):e37–e46. https://​doi.​org/​10.​1016/​S2352-3026(14)70018-3 CrossRefPubMed
16.
go back to reference Raskob GE, van Es N, Segers A, Angchaisuksiri P, Oh D, Boda Z, Lyons RM, Meijer K, Gudz I, Weitz JI, Zhang G, Lanz H, Mercuri MF, Buller HR, VTEi H (2016) Edoxaban for venous thromboembolism in patients with cancer: results from a non-inferiority subgroup analysis of the Hokusai-VTE randomised, double-blind, double-dummy trial. Lancet Haematol 3(8):e379–e387. https://doi.org/10.1016/S2352-3026(16)30057-6 CrossRefPubMed Raskob GE, van Es N, Segers A, Angchaisuksiri P, Oh D, Boda Z, Lyons RM, Meijer K, Gudz I, Weitz JI, Zhang G, Lanz H, Mercuri MF, Buller HR, VTEi H (2016) Edoxaban for venous thromboembolism in patients with cancer: results from a non-inferiority subgroup analysis of the Hokusai-VTE randomised, double-blind, double-dummy trial. Lancet Haematol 3(8):e379–e387. https://​doi.​org/​10.​1016/​S2352-3026(16)30057-6 CrossRefPubMed
20.
go back to reference Schulman S, Kearon C, Subcommittee on Control of Anticoagulation of the S, Standardization Committee of the International Society on T, Haemostasis (2005) Definition of major bleeding in clinical investigations of antihemostatic medicinal products in non-surgical patients. J Thrombosis Haemostasis: JTH 3(4):692–694. https://doi.org/10.1111/j.1538-7836.2005.01204.x CrossRef Schulman S, Kearon C, Subcommittee on Control of Anticoagulation of the S, Standardization Committee of the International Society on T, Haemostasis (2005) Definition of major bleeding in clinical investigations of antihemostatic medicinal products in non-surgical patients. J Thrombosis Haemostasis: JTH 3(4):692–694. https://​doi.​org/​10.​1111/​j.​1538-7836.​2005.​01204.​x CrossRef
21.
go back to reference Investigators E, Bauersachs R, Berkowitz SD, Brenner B, Buller HR, Decousus H, Gallus AS, Lensing AW, Misselwitz F, Prins MH, Raskob GE, Segers A, Verhamme P, Wells P, Agnelli G, Bounameaux H, Cohen A, Davidson BL, Piovella F, Schellong S (2010) Oral rivaroxaban for symptomatic venous thromboembolism. N Engl J Med 363(26):2499–2510. https://doi.org/10.1056/NEJMoa1007903 CrossRef Investigators E, Bauersachs R, Berkowitz SD, Brenner B, Buller HR, Decousus H, Gallus AS, Lensing AW, Misselwitz F, Prins MH, Raskob GE, Segers A, Verhamme P, Wells P, Agnelli G, Bounameaux H, Cohen A, Davidson BL, Piovella F, Schellong S (2010) Oral rivaroxaban for symptomatic venous thromboembolism. N Engl J Med 363(26):2499–2510. https://​doi.​org/​10.​1056/​NEJMoa1007903 CrossRef
22.
go back to reference Hokusai VTEI, Buller HR, Decousus H, Grosso MA, Mercuri M, Middeldorp S, Prins MH, Raskob GE, Schellong SM, Schwocho L, Segers A, Shi M, Verhamme P, Wells P (2013) Edoxaban versus warfarin for the treatment of symptomatic venous thromboembolism. N Engl J Med 369(15):1406–1415. https://doi.org/10.1056/NEJMoa1306638 CrossRef Hokusai VTEI, Buller HR, Decousus H, Grosso MA, Mercuri M, Middeldorp S, Prins MH, Raskob GE, Schellong SM, Schwocho L, Segers A, Shi M, Verhamme P, Wells P (2013) Edoxaban versus warfarin for the treatment of symptomatic venous thromboembolism. N Engl J Med 369(15):1406–1415. https://​doi.​org/​10.​1056/​NEJMoa1306638 CrossRef
25.
go back to reference Lee AY, Levine MN, Baker RI, Bowden C, Kakkar AK, Prins M, Rickles FR, Julian JA, Haley S, Kovacs MJ, Gent M, Randomized comparison of low-molecular-weight heparin versus oral anticoagulant therapy for the prevention of recurrent venous thromboembolism in patients with cancer I (2003) Low-molecular-weight heparin versus a coumarin for the prevention of recurrent venous thromboembolism in patients with cancer. N Engl J Med 349(2):146–153. https://doi.org/10.1056/NEJMoa025313 CrossRefPubMed Lee AY, Levine MN, Baker RI, Bowden C, Kakkar AK, Prins M, Rickles FR, Julian JA, Haley S, Kovacs MJ, Gent M, Randomized comparison of low-molecular-weight heparin versus oral anticoagulant therapy for the prevention of recurrent venous thromboembolism in patients with cancer I (2003) Low-molecular-weight heparin versus a coumarin for the prevention of recurrent venous thromboembolism in patients with cancer. N Engl J Med 349(2):146–153. https://​doi.​org/​10.​1056/​NEJMoa025313 CrossRefPubMed
27.
go back to reference van Es N, Di Nisio M, Bleker SM, Segers A, Mercuri MF, Schwocho L, Kakkar A, Weitz JI, Beyer-Westendorf J, Boda Z, Carrier M, Chlumsky J, Decousus H, Garcia D, Gibbs H, Kamphuisen PW, Monreal M, Ockelford P, Pabinger I, Verhamme P, Grosso MA, Buller HR, Raskob GE (2015) Edoxaban for treatment of venous thromboembolism in patients with cancer. Rationale and design of the Hokusai VTE-cancer study. Thromb Haemost 114(6):1268–1276. https://doi.org/10.1160/TH15-06-0452 CrossRefPubMed van Es N, Di Nisio M, Bleker SM, Segers A, Mercuri MF, Schwocho L, Kakkar A, Weitz JI, Beyer-Westendorf J, Boda Z, Carrier M, Chlumsky J, Decousus H, Garcia D, Gibbs H, Kamphuisen PW, Monreal M, Ockelford P, Pabinger I, Verhamme P, Grosso MA, Buller HR, Raskob GE (2015) Edoxaban for treatment of venous thromboembolism in patients with cancer. Rationale and design of the Hokusai VTE-cancer study. Thromb Haemost 114(6):1268–1276. https://​doi.​org/​10.​1160/​TH15-06-0452 CrossRefPubMed
29.
go back to reference Mantha S, Laube E, Miao Y, Sarasohn DM, Parameswaran R, Stefanik S, Brar G, Samedy P, Wills J, Harnicar S, Soff GA (2017) Safe and effective use of rivaroxaban for treatment of cancer-associated venous thromboembolic disease: a prospective cohort study. J Thromb Thrombolysis 43(2):166–171. https://doi.org/10.1007/s11239-016-1429-1 CrossRefPubMed Mantha S, Laube E, Miao Y, Sarasohn DM, Parameswaran R, Stefanik S, Brar G, Samedy P, Wills J, Harnicar S, Soff GA (2017) Safe and effective use of rivaroxaban for treatment of cancer-associated venous thromboembolic disease: a prospective cohort study. J Thromb Thrombolysis 43(2):166–171. https://​doi.​org/​10.​1007/​s11239-016-1429-1 CrossRefPubMed
30.
go back to reference Pignataro BS, Nishinari K, Cavalcante RN, Centofanti G, Yazbek G, Krutman M, Bomfim GA, Fonseca IY, Teivelis MP, Wolosker N, Sanches SM, Ramacciotti E (2016) Oral rivaroxaban for the treatment of symptomatic venous thromboembolism in 400 patients with active cancer. Clin Appl Thrombosis/Hemostasis. https://doi.org/10.1177/1076029616677800 Pignataro BS, Nishinari K, Cavalcante RN, Centofanti G, Yazbek G, Krutman M, Bomfim GA, Fonseca IY, Teivelis MP, Wolosker N, Sanches SM, Ramacciotti E (2016) Oral rivaroxaban for the treatment of symptomatic venous thromboembolism in 400 patients with active cancer. Clin Appl Thrombosis/Hemostasis. https://​doi.​org/​10.​1177/​1076029616677800​
32.
go back to reference Lyman GH, Bohlke K, Khorana AA, Kuderer NM, Lee AY, Arcelus JI, Balaban EP, Clarke JM, Flowers CR, Francis CW, Gates LE, Kakkar AK, Key NS, Levine MN, Liebman HA, Tempero MA, Wong SL, Somerfield MR, Falanga A, American Society of Clinical O (2015) Venous thromboembolism prophylaxis and treatment in patients with cancer: American Society of Clinical Oncology clinical practice guideline update 2014. J Clin Oncol 33(6):654–656. https://doi.org/10.1200/JCO.2014.59.7351 CrossRefPubMedPubMedCentral Lyman GH, Bohlke K, Khorana AA, Kuderer NM, Lee AY, Arcelus JI, Balaban EP, Clarke JM, Flowers CR, Francis CW, Gates LE, Kakkar AK, Key NS, Levine MN, Liebman HA, Tempero MA, Wong SL, Somerfield MR, Falanga A, American Society of Clinical O (2015) Venous thromboembolism prophylaxis and treatment in patients with cancer: American Society of Clinical Oncology clinical practice guideline update 2014. J Clin Oncol 33(6):654–656. https://​doi.​org/​10.​1200/​JCO.​2014.​59.​7351 CrossRefPubMedPubMedCentral
34.
go back to reference Farge D, Bounameaux H, Brenner B, Cajfinger F, Debourdeau P, Khorana AA, Pabinger I, Solymoss S, Douketis J, Kakkar A (2016) International clinical practice guidelines including guidance for direct oral anticoagulants in the treatment and prophylaxis of venous thromboembolism in patients with cancer. Lancet Oncol 17(10):e452–e466. https://doi.org/10.1016/S1470-2045(16)30369-2 CrossRefPubMed Farge D, Bounameaux H, Brenner B, Cajfinger F, Debourdeau P, Khorana AA, Pabinger I, Solymoss S, Douketis J, Kakkar A (2016) International clinical practice guidelines including guidance for direct oral anticoagulants in the treatment and prophylaxis of venous thromboembolism in patients with cancer. Lancet Oncol 17(10):e452–e466. https://​doi.​org/​10.​1016/​S1470-2045(16)30369-2 CrossRefPubMed
43.
go back to reference Heidbuchel H, Verhamme P, Alings M, Antz M, Hacke W, Oldgren J, Sinnaeve P, Camm AJ, Kirchhof P, European Heart Rhythm A (2013) European Heart Rhythm Association Practical Guide on the use of new oral anticoagulants in patients with non-valvular atrial fibrillation. Europace 15(5):625–651. https://doi.org/10.1093/europace/eut083 CrossRefPubMed Heidbuchel H, Verhamme P, Alings M, Antz M, Hacke W, Oldgren J, Sinnaeve P, Camm AJ, Kirchhof P, European Heart Rhythm A (2013) European Heart Rhythm Association Practical Guide on the use of new oral anticoagulants in patients with non-valvular atrial fibrillation. Europace 15(5):625–651. https://​doi.​org/​10.​1093/​europace/​eut083 CrossRefPubMed
46.
go back to reference Pollack CV Jr, Reilly PA, Eikelboom J, Glund S, Verhamme P, Bernstein RA, Dubiel R, Huisman MV, Hylek EM, Kamphuisen PW, Kreuzer J, Levy JH, Sellke FW, Stangier J, Steiner T, Wang B, Kam CW, Weitz JI (2015) Idarucizumab for dabigatran reversal. N Engl J Med 373(6):511–520. https://doi.org/10.1056/NEJMoa1502000 CrossRefPubMed Pollack CV Jr, Reilly PA, Eikelboom J, Glund S, Verhamme P, Bernstein RA, Dubiel R, Huisman MV, Hylek EM, Kamphuisen PW, Kreuzer J, Levy JH, Sellke FW, Stangier J, Steiner T, Wang B, Kam CW, Weitz JI (2015) Idarucizumab for dabigatran reversal. N Engl J Med 373(6):511–520. https://​doi.​org/​10.​1056/​NEJMoa1502000 CrossRefPubMed
47.
go back to reference Connolly SJ, Milling TJ Jr, Eikelboom JW, Gibson CM, Curnutte JT, Gold A, Bronson MD, Lu G, Conley PB, Verhamme P, Schmidt J, Middeldorp S, Cohen AT, Beyer-Westendorf J, Albaladejo P, Lopez-Sendon J, Goodman S, Leeds J, Wiens BL, Siegal DM, Zotova E, Meeks B, Nakamya J, Lim WT, Crowther M, Investigators A (2016) Andexanet alfa for acute major bleeding associated with factor Xa inhibitors. N Engl J Med 375(12):1131–1141. https://doi.org/10.1056/NEJMoa1607887 CrossRefPubMedPubMedCentral Connolly SJ, Milling TJ Jr, Eikelboom JW, Gibson CM, Curnutte JT, Gold A, Bronson MD, Lu G, Conley PB, Verhamme P, Schmidt J, Middeldorp S, Cohen AT, Beyer-Westendorf J, Albaladejo P, Lopez-Sendon J, Goodman S, Leeds J, Wiens BL, Siegal DM, Zotova E, Meeks B, Nakamya J, Lim WT, Crowther M, Investigators A (2016) Andexanet alfa for acute major bleeding associated with factor Xa inhibitors. N Engl J Med 375(12):1131–1141. https://​doi.​org/​10.​1056/​NEJMoa1607887 CrossRefPubMedPubMedCentral
48.
go back to reference Raval AN, Cigarroa JE, Chung MK, Diaz-Sandoval LJ, Diercks D, Piccini JP, Jung HS, Washam JB, Welch BG, Zazulia AR, Collins SP, American Heart Association Clinical Pharmacology Subcommittee of the Acute Cardiac C, General Cardiology Committee of the Council on Clinical C, Council on Cardiovascular Disease in the Y, Council on Quality of C, Outcomes R (2017) Management of patients on non-vitamin K antagonist oral anticoagulants in the acute care and periprocedural setting: a scientific statement from the American Heart Association. Circulation 135(10):e604–e633. https://doi.org/10.1161/CIR.0000000000000477 CrossRefPubMed Raval AN, Cigarroa JE, Chung MK, Diaz-Sandoval LJ, Diercks D, Piccini JP, Jung HS, Washam JB, Welch BG, Zazulia AR, Collins SP, American Heart Association Clinical Pharmacology Subcommittee of the Acute Cardiac C, General Cardiology Committee of the Council on Clinical C, Council on Cardiovascular Disease in the Y, Council on Quality of C, Outcomes R (2017) Management of patients on non-vitamin K antagonist oral anticoagulants in the acute care and periprocedural setting: a scientific statement from the American Heart Association. Circulation 135(10):e604–e633. https://​doi.​org/​10.​1161/​CIR.​0000000000000477​ CrossRefPubMed
Metadata
Title
The role of direct oral anticoagulants in cancer-related venous thromboembolism: a perspective beyond the guidelines
Author
Cristhiam M. Rojas-Hernandez
Publication date
01-03-2018
Publisher
Springer Berlin Heidelberg
Published in
Supportive Care in Cancer / Issue 3/2018
Print ISSN: 0941-4355
Electronic ISSN: 1433-7339
DOI
https://doi.org/10.1007/s00520-017-3990-3

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