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DOI: 10.1055/a-1886-5991
Treatment and Bleeding Complications of Cancer-Associated Venous Thromboembolism: A Korean Population-Based Study
Funding None.
Abstract
Objectives This study investigated the treatment pattern and the rate of bleeding complications in real-world practice in cancer-associated venous thromboembolism (CT) patients.
Methods We used the Korean Health Insurance Review and Assessment Service database (2014–2018). Among patients with venous thromboembolism, patients with concomitant malignancy diagnostic codes were categorized as CT, while all others were categorized as non-CT. Treatments were categorized as direct oral anticoagulant (DOAC), parenteral anticoagulant (PAC), warfarin, and mixed anticoagulants.
Results We identified 27,205 CT and 57,711 non-CT patients. DOACs were the most frequently used anticoagulants. The proportion of patients treated with PAC was higher in CT than in non-CT patients (35.7 vs. 19.5%; p < 0.01). In CT, the cumulative incidence of any/major bleeding was higher with DOAC (8.1%/3.9%) than with PAC (7.5%/3.2%; p = 0.04 and 0.01, respectively). However, there was no difference in major bleeding when compared with warfarin (p = 0.11) or mixed anticoagulants (p = 0.94). Overall, gastrointestinal (GI) cancer patients showed higher risks of bleeding. The cumulative incidence of major GI bleeding was higher with DOAC than with PAC (4.9 vs. 3.0%; p < 0.01), while there was no difference compared with warfarin (p = 0.59) or mixed anticoagulants (p = 0.80). Major bleeding with each DOAC showed no difference among entire CT (p = 0.94), GI cancer (p = 0.27), and genitourinary cancer (p = 0.88) patients.
Conclusion Five years after their introduction into clinical practice, DOACs have become the most prescribed anticoagulant in Korea. In our patient population, bleeding complications occurred more frequently in CT than in non-CT, especially in patients treated with DOACs.
Keywords
anticoagulants - hemorrhage - heparin - low-molecular-weight heparin - venous thromboembolismAuthor Contributions
S.-A.K. and S.-M.B. drafted the article. S.-A.K., J.H.L., and S.-M.B. contributed to the acquisition, analysis, and interpretation of data. J.Y.L., H.-G.H., Y.-K.K, H.-Y.Y., J.H., J.-O. L., and S.-M.B. revised the manuscript critically for important intellectual content. S.-A.K., J. H.L., J.Y.L., H.-G.H., Y.-K.K., H.-Y.Y., J.H., J.-O.L., and S.-M.B. approved the final version of the manuscript for publication.
Publication History
Received: 21 November 2021
Accepted: 25 June 2022
Accepted Manuscript online:
28 June 2022
Article published online:
28 October 2022
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References
- 1 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
- 2 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
- 3 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
- 4 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
- 5 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
- 6 Thapa N, Shatzel J, Deloughery TG, Olson SR. Direct oral anticoagulants in gastrointestinal malignancies: is the convenience worth the risk?. J Gastrointest Oncol 2019; 10 (04) 807-809
- 7 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
- 8 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
- 9
Farge D,
Frere C,
Connors JM.
et al;
International Initiative on Thrombosis and Cancer (ITAC) advisory panel.
2019 international clinical practice guidelines for the treatment and prophylaxis
of venous thromboembolism in patients with cancer. Lancet Oncol 2019; 20 (10) e566-e581
MissingFormLabel
- 10 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
- 11 National CCancer Network. Cancer-associated venous thromboembolic disease (version 1, 2021). Accessed July 27, 2021 at: https://www.nccn.org/professionals/physician_gls/pdf/vte.pdf
- 12 Kim SA, Yhim HY, Bang SM. Current management of cancer-associated venous thromboembolism: focus on direct oral anticoagulants. J Korean Med Sci 2019; 34 (06) e52
- 13 Angchaisuksiri P, Goto S, Farjat AE. et al. Venous thromboembolism in Asia and worldwide: emerging insights from GARFIELD-VTE. Thromb Res 2021; 201: 63-72
- 14 Kim JA, Yoon S, Kim LY, Kim DS. Towards actualizing the value potential of Korea Health Insurance Review and Assessment (HIRA) data as a resource for health research: strengths, limitations, applications, and strategies for optimal use of HIRA data. J Korean Med Sci 2017; 32 (05) 718-728
- 15 LifeSemantics. Korean standard classification of disease. Accessed July 27 2021 at: https://www.kcdcode.kr/browse/main/
- 16 Lee SR, Choi EK, Han KD, Jung JH, Oh S, Lip GYH. Edoxaban in Asian patients with atrial fibrillation: effectiveness and safety. J Am Coll Cardiol 2018; 72 (08) 838-853
- 17 Hong J, Lee JH, Yhim HY. et al. Incidence of venous thromboembolism in Korea from 2009 to 2013. PLoS One 2018; 13 (01) e0191897
- 18 Khorana AA. Venous thromboembolism and prognosis in cancer. Thromb Res 2010; 125 (06) 490-493
- 19 Cohen AT, Katholing A, Rietbrock S, Bamber L, Martinez C. Epidemiology of first and recurrent venous thromboembolism in patients with active cancer. A population-based cohort study. Thromb Haemost 2017; 117 (01) 57-65
- 20 Haykal T, Zayed Y, Deliwala S. et al. Direct oral anticoagulant versus low-molecular-weight heparin for treatment of venous thromboembolism in cancer patients: an updated meta-analysis of randomized controlled trials. Thromb Res 2020; 194: 57-65
- 21 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
- 22 Angelini DE, Attia D, Wei W. et al. Bleeding outcomes of gastrointestinal cancer patients treated with direct oral anticoagulants vs. low molecular weight heparin. Blood 2020; 136 (Suppl 1): 27
- 23 Houghton DE, Bott-Kitslaar DM, Vargas E. et al. Cancer-associated thrombosis and bleeding risk in gastrointestinal malignancies with apixaban and rivaroxaban compared to low molecular weight heparin. Blood 2018; 132 (Suppl 1): 362
- 24 National Cancer Center.. Annual report of cancer statistics in Korea in 2018. Accessed July 01 2021 at: https://ncc.re.kr/cancerStatsView.ncc?bbsnum=558&searchKey=total&searchValue=&pageNum=1
- 25 Abraham NS, Noseworthy PA, Yao X, Sangaralingham LR, Shah ND. Gastrointestinal safety of direct oral anticoagulants: a large population-based study. Gastroenterology 2017; 152 (05) 1014-1022
- 26 Radadiya D, Devani K, Brahmbhatt B, Reddy C. Major gastrointestinal bleeding risk with direct oral anticoagulants: does type and dose matter? - A systematic review and network meta-analysis. Eur J Gastroenterol Hepatol 2021; 33 (1S, Suppl 1): e50-e58
- 27 Song X, Liu Z, Zeng R. et al. Treatment of venous thromboembolism in cancer patients: a systematic review and meta-analysis on the efficacy and safety of different direct oral anticoagulants (DOACs). Ann Transl Med 2021; 9 (02) 162
- 28 Wysokinski WE, Houghton DE, Casanegra AI. et al. Comparison of apixaban to rivaroxaban and enoxaparin in acute cancer-associated venous thromboembolism. Am J Hematol 2019; 94 (11) 1185-1192