DOAC in the treatment of cancer-associated venous thromboembolism: a retrospective cohort study beyond the guidelines
Tóm tắt
The emerging use of direct oral anticoagulants (DOAC) in the management of cancer-associated venous thromboembolism (CAT) is significantly improving therapeutic adherence and quality of life. Despite this, many conditions can restrict the therapeutic index of these drugs. For all these reasons the latest guidelines recommend the use of heparins in the treatment of CAT as the preferred treatment in some clinical settings. We evaluated the efficacy and the safety of DOAC, in terms of recurrent venous thromboembolism (VTE) and major bleeding (MB), as a composite primary outcome. Mortality and clinically relevant non-major bleeding (CRNMB) were evaluated as secondary outcomes. We performed a retrospective study on 209 patients to compare the effects of DOAC versus heparins for the treatment of CAT. 127 patients with a high bleeding risk neoplasia were enrolled. A primary-outcome event occurred in 11.3% of patients treated with heparins and in 10.5% treated with DOAC (Relative Risk 0.92; 95% CI 0.42–2.01, p = 0.84). Recurrent VTE occurred in 6.1% in the heparins group and in 8.4% in the DOAC group (RR 1.37; 95% CI 0.51–3.64, p = 0.52). MB occurred in 5.2% in the heparins group and in 2.1% in the DOAC group (RR 0.40; 95% CI 0.08–1.93, p = 0.25). DOAC seem to be as effective and safe as heparins in the treatment of CAT. Most bleeding events occurred in patients with high-risk bleeding neoplasms regardless of the type of anticoagulant. Considering the characteristics and satisfaction of patients using DOAC in this setting, this approach should be considered as a first choice.
Tài liệu tham khảo
citation_journal_title=Thromb Haemost; citation_title=Apixaban versus dalteparin for the treatment of acute venous thromboembolism in patients with cancer: the Caravaggio study; citation_author=G Agnelli, C Becattini, R Bauersachs, B Brenner, M Campanini, A Cohen, JM Connors, A Fontanella, G Gussoni, MV Huisman, C Lambert, G Meyer, A Muñoz, JA Sousa, A Torbicki, M Verso, G Vescovo; citation_volume=118; citation_issue=9; citation_publication_date=2018; citation_pages=1668-1678; citation_doi=10.1055/s-0038-1668523; citation_id=CR1
citation_journal_title=JAMA; citation_title=Malignancies, prothrombotic mutations, and the risk of venous thrombosis; citation_author=JW Blom, CJM Doggen, S Osanto, FR Rosendaal; citation_volume=293; citation_issue=6; citation_publication_date=2005; citation_pages=715-722; citation_doi=10.1001/jama.293.6.715; citation_id=CR2
citation_journal_title=Eur Heart J Cardiovasc Pharmacother; citation_title=Efficacy and safety of direct oral anticoagulants vs. low molecular weight heparin for cancer-related venous thromboembolism: a meta-analysis of randomized trials; citation_author=A Elbadawi, M Shnoda, K Mahmoud, IY Elgendy; citation_volume=7; citation_issue=5; citation_publication_date=2021; citation_pages=380-388; citation_doi=10.1093/ehjcvp/pvaa067; citation_id=CR3
citation_journal_title=Lancet Oncol; citation_title=2019 international clinical practice guidelines for the treatment and prophylaxis of venous thromboembolism in patients with cancer; citation_author=D Farge, C Frere, JM Connors, C Ay, AA Khorana, A Munoz, B Brenner, A Kakkar, H Rafii, S Solymoss, D Brilhante, M Monreal, H Bounameaux, I Pabinger, J Douketis; citation_volume=20; citation_issue=10; citation_publication_date=2019; citation_pages=e566-e581; citation_doi=10.1016/S1470-2045(19)30336-5; citation_id=CR4
citation_journal_title=Lancet Oncol; citation_title=Definition and classification of cancer cachexia: an international consensus; citation_author=K Fearon, F Strasser, SD Anker, I Bosaeus, E Bruera, RL Fainsinger, A Jatoi, C Loprinzi, N MacDonald, G Mantovani, M Davis, M Muscaritoli, F Ottery, L Radbruch, P Ravasco, D Walsh, A Wilcock, S Kaasa, VE Baracos; citation_volume=12; citation_issue=5; citation_publication_date=2011; citation_pages=489-495; citation_doi=10.1016/S1470-2045(10)70218-7; citation_id=CR5
citation_journal_title=Cardiovasc Drugs Ther.; citation_title=Impact of polypharmacy and P-glycoprotein- and CYP3A4-modulating drugs on safety and efficacy of oral anticoagulation therapy in patients with atrial fibrillation; citation_author=RE Harskamp, M Teichert, WAM Lucassen, HCPM Weert, RD Lopes; citation_volume=33; citation_issue=5; citation_publication_date=2019; citation_pages=615-623; citation_doi=10.1007/s10557-019-06907-8; citation_id=CR6
citation_journal_title=J Thromb Haemost; citation_title=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; citation_author=S Kaatz, D Ahmad, AC Spyropoulos, S Schulman; citation_volume=13; citation_issue=11; citation_publication_date=2015; citation_pages=2119-2126; citation_doi=10.1111/jth.13140; citation_id=CR7
citation_journal_title=Blood Adv; citation_title=Venous thromboembolism prophylaxis and treatment in patients with cancer: ASCO clinical practice guideline update; citation_author=NS Key, AA Khorana, NM Kuderer, K Bohlke, AYY Lee, JI Arcelus, SL Wong, EP Balaban, CR Flowers, CW Francis, LE Gates, AK Kakkar, MN Levine, HA Liebman, MA Tempero, GH Lyman, A Falanga; citation_volume=5; citation_issue=4; citation_publication_date=2021; citation_pages=927-974; citation_doi=10.1182/bloodadvances.2020003442; citation_id=CR8
citation_journal_title=J Thromb Haemost; citation_title=Thromboembolism is a leading cause of death in cancer patients receiving outpatient chemotherapy; citation_author=AA Khorana, CW Francis, E Culakova, NM Kuderer, GH Lyman; citation_volume=5; citation_issue=3; citation_publication_date=2007; citation_pages=632-634; citation_doi=10.1111/j.1538-7836.2007.02374.x; citation_id=CR9
citation_journal_title=Cancer; citation_title=Frequency, risk factors, and trends for venous thromboembolism among hospitalized cancer patients; citation_author=AA Khorana, CW Francis, E Culakova, NM Kuderer, GH Lyman; citation_volume=110; citation_issue=10; citation_publication_date=2007; citation_pages=2339-2346; citation_doi=10.1002/cncr.23062; citation_id=CR10
citation_journal_title=Cancer; citation_title=Incidence and predictors of venous thromboembolism (VTE) among ambulatory high-risk cancer patients undergoing chemotherapy in the United States; citation_author=AA Khorana, M Dalal, J Lin, GC Connolly; citation_volume=119; citation_issue=3; citation_publication_date=2013; citation_pages=648-655; citation_doi=10.1002/cncr.27772; citation_id=CR11
citation_journal_title=J Thromb Thrombolysis; citation_title=DOAC compared to LMWH in the treatment of cancer related-venous thromboembolism: a systematic review and meta-analysis; citation_author=V Mai, VF Tanguay, CA Guay, L Bertoletti, S Magnan, AF Turgeon, Y Lacasse, JC Lega, S Provencher; citation_volume=50; citation_issue=3; citation_publication_date=2020; citation_pages=661-667; citation_doi=10.1007/s11239-020-02055-1; citation_id=CR12
citation_journal_title=Blood; citation_title=Venous thromboembolism in cancer patients: a population-based cohort study; citation_author=FI Mulder, E Horváth-Puhó, N Es, HWM Laarhoven, L Pedersen, F Moik, C Ay, HR Büller, HT Sørensen; citation_volume=137; citation_issue=14; citation_publication_date=2021; citation_pages=1959-1969; citation_doi=10.1182/blood.2020007338; citation_id=CR13
citation_journal_title=NEJM; citation_title=Edoxaban for the treatment of cancer-associated venous thromboembolism; citation_author=GE Raskob, N Es, P Verhamme, M Carrier, M Nisio, D Garcia, MA Grosso, AK Kakkar, MJ Kovacs, MF Mercuri, G Meyer, A Segers, M Shi, T-F Wang, E Yeo, G Zhang, JI Zwicker, JI Weitz, HR Büller; citation_publication_date=2017; citation_doi=10.1056/NEJMoa1711948; citation_id=CR14
citation_journal_title=J Thromb Haemost; citation_title=Definition of major bleeding in clinical investigations of antihemostatic medicinal products in non-surgical patients; citation_author=S Schulman, C Kearon; citation_volume=3; citation_issue=4; citation_publication_date=2005; citation_pages=692-694; citation_doi=10.1111/j.1538-7836.2005.01204.x; citation_id=CR15
citation_journal_title=Int J Clin Pharmacol Ther; citation_title=The effect of food on the absorption and pharmacokinetics of rivaroxaban; citation_author=J Stampfuss, D Kubitza, M Becka, W Mueck; citation_volume=51; citation_issue=7; citation_publication_date=2013; citation_pages=549-561; citation_doi=10.5414/CP201812; citation_id=CR16
citation_journal_title=J Natl Compr Canc Netw; citation_title=NCCN clinical practice guidelines in oncology; citation_author=MB Streiff, B Holmstrom, D Angelini, A Ashrani, A Elshoury, J Fanikos, KY Fertrin, AE Fogerty, S Gao, SZ Goldhaber, K Gundabolu, I Ibrahim, E Kraut, AD Leavitt, A Lee, JT Lee, M Lim, J Mann, K Martin, B McMahon, J Moriarty, C Morton, TL Ortel, R Paschal, J Schaefer, S Shattil, T Siddiqi, D Sudheendra, E Williams, L Hollinger, MQ Nguyen; citation_volume=19; citation_issue=10; citation_publication_date=2021; citation_pages=1181-1201; citation_doi=10.6004/jnccn.2021.0047; citation_id=CR17
citation_journal_title=Cancers (basel); citation_title=Direct oral anticoagulants in cancer patients time for a change in paradigm; citation_author=MZ Wojtukiewicz, P Skalij, P Tokajuk, B Politynska, AM Wojtukiewicz, SC Tucker, KV Honn; citation_volume=12; citation_issue=5; citation_publication_date=2020; citation_pages=1144; citation_doi=10.3390/cancers12051144; citation_id=CR18
citation_journal_title=J Clin Oncol; citation_title=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); citation_author=AM Young, A Marshall, J Thirlwall, O Chapman, A Lokare, C Hill, D Hale, JA Dunn, GH Lyman, C Hutchinson, P MacCallum, A Kakkar, FDR Hobbs, S Petrou, J Dale, CJ Poole, A Maraveyas, M Levine; citation_volume=36; citation_issue=20; citation_publication_date=2018; citation_pages=2017-2023; citation_doi=10.1200/JCO.2018.78.8034; citation_id=CR19