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DOI: 10.1055/s-0039-1693479
Direct Oral Anticoagulants in Cancer Patients
Publication History
Publication Date:
05 August 2019 (online)
Abstract
Cancer-associated thrombosis (CAT) is a common occurrence in the journey of a cancer patient and its management poses significant challenges. Low molecular weight heparin (LMWH) is the standard of care but the high cost and the inconvenience of daily injections have led to low persistence with therapy. Direct oral anticoagulants (DOACs) are effective and safe for the treatment of venous thromboembolism (VTE) compared with vitamin K antagonist (VKA) therapy in noncancer patients, and emerging data comparing their use with LMWH in CAT are rapidly changing clinical practice. Recent randomized controlled trials also reported that specific DOACs are effective for primary prevention of CAT in patients undergoing systemic cancer therapy, but this benefit might be offset by an increased risk of bleeding. Undoubtedly, the option of an effective and safe oral anticoagulant is appealing to physicians and patients but critical limitations of DOACs, particularly bleeding and drug-drug interaction, need careful consideration. Understanding the scientific data, as well as each patient's preferences and values, are paramount in individualizing therapy in this special population of patients. This review summarizes the current evidence for DOACs for the treatment and prevention of CAT, discusses the importance of careful patient selection, and highlights upcoming new studies that will inform guideline recommendations.
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References
- 1 Trousseau A. Phlegmasia alba dolens. In: Lectures on Clinical Medicine, Delivered at the Hotel-Dieu, Paris. Vol. 5. London, England: New Sydenham Society; 1865: 281-332
- 2 Heit JA, Silverstein MD, Mohr DN, Petterson TM, O'Fallon WM, Melton III LJ. Risk factors for deep vein thrombosis and pulmonary embolism: a population-based case-control study. Arch Intern Med 2000; 160 (06) 809-815
- 3 Lee AY. Management of thrombosis in cancer: primary prevention and secondary prophylaxis. Br J Haematol 2005; 128 (03) 291-302
- 4 Khorana AA, Francis CW, Culakova E, Kuderer NM, Lyman GH. Thromboembolism is a leading cause of death in cancer patients receiving outpatient chemotherapy. J Thromb Haemost 2007; 5 (03) 632-634
- 5 Arora M, Wun T. Adverse impact of venous thromboembolism on patients with cancer. Semin Thromb Hemost 2014; 40 (03) 313-318
- 6 Kourlaba G, Relakis J, Mylonas C. , et al. The humanistic and economic burden of venous thromboembolism in cancer patients: a systematic review. Blood Coagul Fibrinolysis 2015; 26 (01) 13-31
- 7 Timp JF, Braekkan SK, Versteeg HH, Cannegieter SC. Epidemiology of cancer-associated venous thrombosis. Blood 2013; 122 (10) 1712-1723
- 8 Prandoni P, Lensing AW, Piccioli A. , et al. Recurrent venous thromboembolism and bleeding complications during anticoagulant treatment in patients with cancer and venous thrombosis. Blood 2002; 100 (10) 3484-3488
- 9 Lee AY, Levine MN, Baker RI. , et al; Randomized Comparison of Low-Molecular-Weight Heparin versus Oral Anticoagulant Therapy for the Prevention of Recurrent Venous Thromboembolism in Patients with Cancer (CLOT) Investigators. Low-molecular-weight heparin versus a coumarin for the prevention of recurrent venous thromboembolism in patients with cancer. N Engl J Med 2003; 349 (02) 146-153
- 10 Lee AYY, Kamphuisen PW, Meyer G. , et al; CATCH Investigators. Tinzaparin vs warfarin for treatment of acute venous thromboembolism in patients with active cancer: a randomized clinical trial. JAMA 2015; 314 (07) 677-686
- 11 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 (15) 1729-1735
- 12 Deitcher SR, Kessler CM, Merli G, Rigas JR, Lyons RM, Fareed J. ; ONCENOX Investigators. 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 2006; 12 (04) 389-396
- 13 Carrier M, Cameron C, Delluc A, Castellucci L, Khorana AA, Lee AY. Efficacy and safety of anticoagulant therapy for the treatment of acute cancer-associated thrombosis: a systematic review and meta-analysis. Thromb Res 2014; 134 (06) 1214-1219
- 14 Kahale LA, Hakoum MB, Tsolakian IG. , et al. Anticoagulation for the long-term treatment of venous thromboembolism in people with cancer. Cochrane Database Syst Rev 2018; 6: CD006650
- 15 Kearon C, Akl EA, Ornelas J. , et al. Antithrombotic therapy for VTE disease: CHEST guideline and expert panel report. Chest 2016; 149 (02) 315-352
- 16 Lyman GH, Bohlke K, Khorana AA. , et al; American Society of Clinical Oncology. Venous thromboembolism prophylaxis and treatment in patients with cancer: american society of clinical oncology clinical practice guideline update 2014. J Clin Oncol 2015; 33 (06) 654-656
- 17 Mandalà M, Labianca R. ; European Society for Medical Oncology. Venous thromboembolism (VTE) in cancer patients. ESMO clinical recommendations for prevention and management. Thromb Res 2010; 125 (Suppl. 02) S117-S119
- 18 Khorana AA, Yannicelli D, McCrae KR. , et al. Evaluation of US prescription patterns: Are treatment guidelines for cancer-associated venous thromboembolism being followed?. Thromb Res 2016; 145: 51-53
- 19 Khorana AA, McCrae KR, Milentijevic D. , et al. Current practice patterns and patient persistence with anticoagulant treatments for cancer-associated thrombosis. Res Pract Thromb Haemost 2017; 1 (01) 14-22
- 20 Ansell J, Hirsh J, Hylek E, Jacobson A, Crowther M, Palareti G. Pharmacology and management of the vitamin K antagonists: American College of Chest Physicians Evidence-Based Clinical Practice Guidelines (8th Edition). Chest 2008; 133 (6 Suppl): 160S-198S
- 21 Agnelli G, Buller HR, Cohen A. , et al; AMPLIFY Investigators. Oral apixaban for the treatment of acute venous thromboembolism. N Engl J Med 2013; 369 (09) 799-808
- 22 Büller HR, Décousus H, Grosso MA. , et al; Hokusai-VTE Investigators. Edoxaban versus warfarin for the treatment of symptomatic venous thromboembolism. N Engl J Med 2013; 369 (15) 1406-1415
- 23 Bauersachs R, Berkowitz SD, Brenner B. , et al; EINSTEIN Investigators. Oral rivaroxaban for symptomatic venous thromboembolism. N Engl J Med 2010; 363 (26) 2499-2510
- 24 Büller HR, Prins MH, Lensin AW. , et al; EINSTEIN–PE Investigators. Oral rivaroxaban for the treatment of symptomatic pulmonary embolism. N Engl J Med 2012; 366 (14) 1287-1297
- 25 Schulman S, Kearon C, Kakkar AK. , et al; RE-COVER Study Group. Dabigatran versus warfarin in the treatment of acute venous thromboembolism. N Engl J Med 2009; 361 (24) 2342-2352
- 26 van der Hulle T, den Exter PL, Kooiman J, van der Hoeven JJ, Huisman MV, Klok FA. Meta-analysis of the efficacy and safety of new oral anticoagulants in patients with cancer-associated acute venous thromboembolism. J Thromb Haemost 2014; 12 (07) 1116-1120
- 27 Raskob GE, van Es N, Verhamme P. , et al; Hokusai VTE Cancer Investigators. Edoxaban for the treatment of cancer-associated venous thromboembolism. N Engl J Med 2018; 378 (07) 615-624
- 28 Kraaijpoel N, Di Nisio M, Mulder FI. , et al. Clinical impact of bleeding in cancer-associated venous thromboembolism: results from the hokusai vte cancer study. Thromb Haemost 2018; 118 (08) 1439-1449
- 29 Eerenberg ES, Middeldorp S, Levi M, Lensing AW, Büller HR. Clinical impact and course of major bleeding with rivaroxaban and vitamin K antagonists. J Thromb Haemost 2015; 13 (09) 1590-1596
- 30 Young AM, 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 (SELECT-D). J Clin Oncol 2018; 36 (20) 2017-2023
- 31 McBane Ii R, Loprinzi CL, Ashrani A. , et al. Apixaban and dalteparin in active malignancy associated venous thromboembolism. The ADAM VTE Trial. Thromb Haemost 2017; 117 (10) 1952-1961
- 32 McBane Ii R. Apixaban, Dalteparin, in Active Cancer Associated Venous Thromboembolism, the ADAM VTE Trial. Blood Adv 2018; 132 (Suppl. 01) 421
- 33 Agnelli G, Becattini C, Bauersachs R. , et al; Caravaggio Study Investigators. Apixaban versus dalteparin for the treatment of acute venous thromboembolism in patients with cancer: the caravaggio study. Thromb Haemost 2018; 118 (09) 1668-1678
- 34 Assistance Publique–Hôpitaux de Paris B. Cancer associated thrombosis, a pilot treatment study using rivaroxaban (CASTA-DIVA). 2018 . Available from: https://clinicaltrials.gov/ct2/show/NCT02746185 . Accessed March 12, 2019
- 35 Riess H, Sinn M, Kreher S. fur den Arbeitskreis Hamostaseologie der Deutschen Gesellschaft fur Hamatologie und Medizinische O. [CONKO-011: Evaluation of patient satisfaction with the treatment of acute venous thromboembolism with rivaroxaban or low molecular weight heparin in cancer patients. A randomized phase III study]. Dtsch Med Wochenschr 2015; 140 (Suppl . (Suppl. 01) S22-S23
- 36 Alliance Foundation Trials L. Direct oral anticoagulants (DOACs) versus lmwh +/- warfarin for vte in cancer. 2018 . Available from: https://clinicaltrials.gov/ct2/show/NCT02744092 . Accessed March 12, 2019
- 37 Janssen Research and Development LLC B. A non-interventional study on xarelto for treatment of venous thromboembolism (VTE) and prevention of recurrent vte in patients with active cancer (COSIMO). 2018 . Available from: https://clinicaltrials.gov/ct2/show/NCT02742623 . Accessed March 12, 2019
- 38 Spencer FA, Emery C, Lessard D. , et al. The Worcester venous thromboembolism study: a population-based study of the clinical epidemiology of venous thromboembolism. J Gen Intern Med 2006; 21 (07) 722-727
- 39 Agnelli G, George DJ, Kakkar AK. , et al; SAVE-ONCO Investigators. Semuloparin for thromboprophylaxis in patients receiving chemotherapy for cancer. N Engl J Med 2012; 366 (07) 601-609
- 40 Agnelli G, Gussoni G, Bianchini C. , et al; PROTECHT Investigators. Nadroparin for the prevention of thromboembolic events in ambulatory patients with metastatic or locally advanced solid cancer receiving chemotherapy: a randomised, placebo-controlled, double-blind study. Lancet Oncol 2009; 10 (10) 943-949
- 41 Khorana AA, Soff GA, Kakkar AK. , et al; CASSINI Investigators. Rivaroxaban for thromboprophylaxis in high-risk ambulatory patients with cancer. N Engl J Med 2019; 380 (08) 720-728
- 42 Khorana AA, Kuderer NM, Culakova E, Lyman GH, Francis CW. Development and validation of a predictive model for chemotherapy-associated thrombosis. Blood 2008; 111 (10) 4902-4907
- 43 Chaudhury A, Balakrishnan A, Thai C. , et al. Validation of the Khorana score in a large cohort of cancer patients with venous thromboembolism. Blood 2016; 128: 879
- 44 Carrier M, Abou-Nassar K, Mallick R. , et al; AVERT Investigators. Apixaban to prevent venous thromboembolism in patients with cancer. N Engl J Med 2019; 380 (08) 711-719
- 45 Ageno W, Gallus AS, Wittkowsky A, Crowther M, Hylek EM, Palareti G. Oral anticoagulant therapy: Antithrombotic Therapy and Prevention of Thrombosis, 9th ed: American College of Chest Physicians Evidence-Based Clinical Practice Guidelines. Chest 2012; 141 (2, Suppl.): e44S-e88S
- 46 Vazquez SR. Drug-drug interactions in an era of multiple anticoagulants: a focus on clinically relevant drug interactions. Blood 2018; 132 (21) 2230-2239
- 47 Samuelson Bannow BT, Lee A, Khorana AA. , et al. Management of cancer-associated thrombosis in patients with thrombocytopenia: guidance from the SSC of the ISTH. J Thromb Haemost 2018; 16 (06) 1246-1249
- 48 Carrier M, Lazo-Langner A, Shivakumar S. , et al. Clinical challenges in patients with cancer-associated thrombosis: Canadian expert consensus recommendations. Curr Oncol 2015; 22 (01) 49-59
- 49 Heit JA, Mohr DN, Silverstein MD, Petterson TM, O'Fallon WM, Melton III LJ. Predictors of recurrence after deep vein thrombosis and pulmonary embolism: a population-based cohort study. Arch Intern Med 2000; 160 (06) 761-768
- 50 Chee CE, Ashrani AA, Marks RS. , et al. Predictors of venous thromboembolism recurrence and bleeding among active cancer patients: a population-based cohort study. Blood 2014; 123 (25) 3972-3978
- 51 Chin-Yee N, Tanuseputro P, Carrier M, Noble S. Thromboembolic disease in palliative and end-of-life care: a narrative review. Thromb Res 2019; 175: 84-89
- 52 Carrier M, Blais N, Crowther M. , et al. Treatment algorithm in cancer-associated thrombosis: Canadian expert consensus. Curr Oncol 2018; 25 (05) 329-337
- 53 Khorana AA, Noble S, Lee AYY. , et al. Role of direct oral anticoagulants in the treatment of cancer-associated venous thromboembolism: guidance from the SSC of the ISTH. J Thromb Haemost 2018; 16 (09) 1891-1894
- 54 Streiff MB, Holmstrom B, Angelini D. , et al. Guidelines Insights: Cancer-Associated Venous Thromboembolic Disease. Version 2.2018. J Natl Compr Canc Netw 2018; 16 (11) 1289-1303
- 55 Francis CW, Kessler CM, Goldhaber SZ. , et al. Treatment of venous thromboembolism in cancer patients with dalteparin for up to 12 months: the DALTECAN Study. J Thromb Haemost 2015; 13 (06) 1028-1035
- 56 Jara-Palomares L, Solier-Lopez A, Elias-Hernandez T. , et al. Tinzaparin in cancer associated thrombosis beyond 6months: TiCAT study. Thromb Res 2017; 157: 90-96
- 57 Kovacs MJ, Kahn SR, Rodger M. , et al. A pilot study of central venous catheter survival in cancer patients using low-molecular-weight heparin (dalteparin) and warfarin without catheter removal for the treatment of upper extremity deep vein thrombosis (The Catheter Study). J Thromb Haemost 2007; 5 (08) 1650-1653
- 58 Delluc A, Le Gal G, Scarvelis D, Carrier M. Outcome of central venous catheter associated upper extremity deep vein thrombosis in cancer patients. Thromb Res 2015; 135 (02) 298-302
- 59 Davies GA, Lazo-Langner A, Gandara E. , et al. A prospective study of Rivaroxaban for central venous catheter associated upper extremity deep vein thrombosis in cancer patients (catheter 2). Thromb Res 2018; 162: 88-92