Real-world Data on Treatment Patterns and Bleeding in Cancer-associated Thrombosis: Data from the TROLL Registry

Abstract

Background International guidelines are increasingly recommending direct oral anticoagulants (DOACs) as the first-line treatment for cancer-associated thrombosis (CAT). However, data regarding treatment patterns and adherence to guidelines in patients with CAT are scarce.

Objectives This study aimed to explore anticoagulant treatment patterns in patients with CAT and to calculate the incidence rates of bleeding events.

Methods Patients ≥18 years with active cancer and a first-time venous thromboembolism between 2005 and 2020 were identified through the Venous Thrombosis Registry in ØstfOLd HospitaL. Outcome measures were patterns of anticoagulant treatment during the study period and bleeding events. We calculated overall incidence rates per 100 person-years and 6- and 12-month cumulative incidence of major and clinically relevant nonmajor bleeding (CRNMB) during anticoagulant treatment.

Results Median age of 842 CAT patients at the time of thrombosis was 69 years (interquartile range 61–77), and 443 (52.6%) were men. In total, 526 patients (62.5%) had pulmonary embolism and 255 (30.3%) had deep vein thrombosis. Low molecular weight heparin (LMWH) was prescribed to 713 (85.8%) patients, whereas 64 (7.7%) received DOACs and 54 (6.5%) received vitamin K antagonists as the initial anticoagulant treatment. Prescription of DOACs as initial treatment increased from 3.0% in 2013/2014 to 18.0% in 2019/2020. The incidence rate of major bleeding was 6.9 (95% confidence interval [CI] 5.2–9.2) and 10.1 (95% CI 8.0–12.9) in CRNMB.

Conclusion Most patients were treated with LMWH. However, a gradual shift in treatment toward DOACs was observed. Overall, bleeding complications were rare and comparable to those reported in randomized trials.

Keywords

cancer-associated thrombosis - venous thromboembolism - bleeding - anticoagulants - direct oral anticoagulants - low molecular weight heparin

• References

• 1 Mulder FI, Horváth-Puhó E, van Es N. et al. Venous thromboembolism in cancer patients: a population-based cohort study. Blood 2021; 137 (14) 1959-1969
• 2 Sørensen HT, Mellemkjaer L, Olsen JH, Baron JA. Prognosis of cancers associated with venous thromboembolism. N Engl J Med 2000; 343 (25) 1846-1850
• 3 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
• 4 Lyman GH, Culakova E, Poniewierski MS, Kuderer NM. Morbidity, mortality and costs associated with venous thromboembolism in hospitalized patients with cancer. Thromb Res 2018; 164 (Suppl. 01) S112-S118
• 5 Sharman Moser S, Spectre G, Raanani P. et al. Cancer-associated venous thromboembolism in Israel: Incidence, risk factors, treatment, and health care utilization in a population based cohort study. Res Pract Thromb Haemost 2022; 6 (04) e12653-e12653
• 6 Prandoni P, Lensing AWA, 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
• 7 Prandoni P, Falanga A, Piccioli A. Cancer and venous thromboembolism. Lancet Oncol 2005; 6 (06) 401-410
• 8 Agnelli G, Becattini C, Meyer G. et al; Caravaggio Investigators. Apixaban for the treatment of venous thromboembolism associated with cancer. N Engl J Med 2020; 382 (17) 1599-1607
• 9 McBane II RD, Wysokinski WE, Le-Rademacher JG. et al. Apixaban and dalteparin in active malignancy-associated venous thromboembolism: The ADAM VTE trial. J Thromb Haemost 2020; 18 (02) 411-421
• 10 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
• 11 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
• 12 Lyman GH, Carrier M, Ay C. et al. American Society of Hematology 2021 guidelines for management of venous thromboembolism: prevention and treatment in patients with cancer. Blood Adv 2021; 5 (04) 927-974
• 13 Key NS, Khorana AA, Kuderer NM. et al. Venous thromboembolism prophylaxis and treatment in patients with cancer: ASCO clinical practice guideline update. J Clin Oncol 2020; 38 (05) 496-520
• 14 Streiff MB, Holmstrom B, Angelini D. et al. Cancer-Associated Venous Thromboembolic Disease, Version 2.2021, NCCN Clinical Practice Guidelines in Oncology. J Natl Compr Canc Netw 2021; 19 (10) 1181-1201
• 15 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
• 16 Farge D, Frere C, Connors JM. et al; International Initiative on Thrombosis and Cancer (ITAC) advisory panel. 2022 International Clinical Practice Guidelines for the treatment and prophylaxis of venous thromboembolism in patients with cancer, including patients with COVID-19. Lancet Oncol 2022; 23 (07) e334-e347
• 17 Jørgensen CT, Tavoly M, Pettersen HH. et al. The venous thrombosis registry in Østfold Hospital (TROLL registry) - design and cohort description. Res Pract Thromb Haemost 2022; 6 (05) E12770
• 18 Kaatz S, Ahmad D, Spyropoulos AC, Schulman S. Subcommittee on Control of Anticoagulation. Definition of clinically relevant non-major bleeding in studies of anticoagulants in atrial fibrillation and venous thromboembolic disease in non-surgical patients: communication from the SSC of the ISTH. J Thromb Haemost 2015; 13 (11) 2119-2126
• 19 Schulman S, Kearon C. Subcommittee on Control of Anticoagulation of the Scientific and Standardization Committee of the International Society on Thrombosis and Haemostasis. Definition of major bleeding in clinical investigations of antihemostatic medicinal products in non-surgical patients. J Thromb Haemost 2005; 3 (04) 692-694
• 20 Stępień K, Nowak K, Zalewski J, Undas A. Non-vitamin K antagonist oral anticoagulants in patients with atrial fibrillation and colorectal cancer: a single–center experience. Kardiol Pol 2019; 77 (12) 1186-1189
• 21 Bertoletti L, Gusto G, Khachatryan A. et al. Anticoagulant treatment patterns and outcomes in patients with venous thromboembolism and active cancer - a nationwide cohort study in France. Blood 2021; 138 (Suppl. 01) 670-670
• 22 Uppuluri EM, Burke KR, Haaf CM, Shapiro NL. Assessment of venous thromboembolism treatment in patients with cancer on low molecular weight heparin, warfarin, and the direct oral anticoagulants. J Oncol Pharm Pract 2019; 25 (02) 261-268
• 23 Kim S-A, Lee JH, Lee JY. et al. Treatment and bleeding complications of cancer-associated venous thromboembolism: a Korean population-based study. Thromb Haemost 2022; 122 (12) 2011-2018
• 24 Phelps MK, Wiczer TE, Erdeljac HP. et al. A single center retrospective cohort study comparing low-molecular-weight heparins to direct oral anticoagulants for the treatment of venous thromboembolism in patients with cancer - a real world experience. J Oncol Pharm Pract 2019; 25 (04) 793-800
• 25 Weitz JI, Haas S, Ageno W. et al; GARFIELD-VTE investigators. Cancer associated thrombosis in everyday practice: perspectives from GARFIELD-VTE. J Thromb Thrombolysis 2020; 50 (02) 267-277
• 26 Stepien K, Nowak K, Zalewski J, Pac A, Undas A. Extended treatment with non-vitamin K antagonist oral anticoagulants versus low-molecular-weight heparins in cancer patients following venous thromboembolism. A pilot study. Vascul Pharmacol 2019; 120: 106567-106567
• 27 Moik F, Colling M, Mahé I, Jara-Palomares L, Pabinger I, Ay C. Extended anticoagulation treatment for cancer-associated thrombosis-Rates of recurrence and bleeding beyond 6 months: a systematic review. J Thromb Haemost 2022; 20 (03) 619-634
• 28 Yamashita Y, Morimoto T, Amano H. et al; COMMAND VTE Registry Investigators. Anticoagulation therapy for venous thromboembolism in the real world-from the COMMAND VTE Registry. Circ J 2018; 82 (05) 1262-1270
• 29 Ross JA, Miller MM, Rojas Hernandez CM. Comparative effectiveness and safety of direct oral anticoagulants (DOACs) versus conventional anticoagulation for the treatment of cancer-related venous thromboembolism: a retrospective analysis. Thromb Res 2017; 150: 86-89
• 30 Awano N, Okano T, Kawachi R. et al. One-year incidences of venous thromboembolism, bleeding, and death in patients with lung cancer (Cancer-VTE Subanalysis). JTO Clin Res Rep 2022; 3 (09) 100392