Antithrombotic secondary prophylaxis with low dose of apixaban or rivaroxaban in the onco-hematologic patients: comparison with non-neoplastic patients.
Antithrombotic secondary prophylaxis
Low-dose apixaban and rivaroxaban
Onco-hematologic patients
Venous thromboembolism in cancer patients
Journal
Annals of hematology
ISSN: 1432-0584
Titre abrégé: Ann Hematol
Pays: Germany
ID NLM: 9107334
Informations de publication
Date de publication:
Sep 2023
Sep 2023
Historique:
received:
10
05
2023
accepted:
11
07
2023
medline:
23
8
2023
pubmed:
22
7
2023
entrez:
21
7
2023
Statut:
ppublish
Résumé
Management of cancer-associated thrombosis (CAT) is usually performed employing low molecular weight heparin (LMWH) or direct oral anticoagulants (DOACs). Low-intensity DOACs are the mainstay for extended duration therapy for VTE in non-oncologic patients. The aim of our study was to evaluate the efficacy and the safety of low doses of apixaban or rivaroxaban as secondary prophylaxis in patients affected by hematological malignancies with follow-up > 12 months. We report an observational, retrospective, single-center study that evaluated consecutive patients referred to our center between January 2016 and January 2023. The DOACs were administered at full dose during the acute phase of VTE and then at low dose for the extended phase. We included 154 patients: 53 patients affected by hematological malignancies compared to 101 non-neoplastic patients. During full-dose treatment, no thrombotic recurrences were observed in the two groups. During low-dose therapy, 2 (1.9%) thrombotic events (tAE) were observed in the control group. During full-dose treatment, the rate of bleeding events (bAE) was 9/154 (5.8%): 6/53 (11%) in hematological patients and 3/101 (2.9%) in non-hematological patients (p = 0.0003). During low-dose therapy, 4/154 (2.6%) bAE were observed: 3/53 (5.5%) in the hematologic group and 1 (1%) in the control group (p = 0.07). We found encouraging data on the safety and efficacy of low doses of DOACs as secondary prophylaxis in the onco-hematologic setting; no thrombotic complications were observed, and the incidence of hemorrhagic events was low.
Identifiants
pubmed: 37479891
doi: 10.1007/s00277-023-05369-1
pii: 10.1007/s00277-023-05369-1
doi:
Substances chimiques
Rivaroxaban
9NDF7JZ4M3
apixaban
3Z9Y7UWC1J
Fibrinolytic Agents
0
Heparin, Low-Molecular-Weight
0
Types de publication
Observational Study
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
2599-2605Informations de copyright
© 2023. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.
Références
Mulder FI, Horváth-Puhó E, van Es N, van Laarhoven HWM, Pedersen L, Moik F et al (2021) Venous thromboembolism in cancer patients: a population-based cohort study. Blood 137(14):1959–1969. https://doi.org/10.1182/blood.2020007338
doi: 10.1182/blood.2020007338
pubmed: 33171494
Moik F, Chan WE, Wiedemann S, Hoeller C, Tuchmann F, Aretin MB et al (2021) Incidence, risk factors, and outcomes of venous and arterial thromboembolism in immune checkpoint inhibitor therapy. Blood 137(12):1669–1678. https://doi.org/10.1182/blood.2020007878
doi: 10.1182/blood.2020007878
pubmed: 33067632
pmcid: 8016631
Moik F, Ay C, Pabinger I (2020) Risk prediction for cancer-associated thrombosis in ambulatory patients with cancer: past, present and future. Thromb Res 191(Suppl 1):S3–S11. https://doi.org/10.1016/S0049-3848(20)30389-3
doi: 10.1016/S0049-3848(20)30389-3
pubmed: 32736775
Prandoni P, Lensing AW, Piccioli A, Bernardi E, Simioni P, Girolami B et al (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
doi: 10.1182/blood-2002-01-0108
pubmed: 12393647
Abdulla A, Davis WM, Ratnaweera N, Szefer E, Ballantyne SB, Lee AYY (2020) A meta-analysis of case fatality rates of recurrent venous thromboembolism and major bleeding in patients with cancer. Thromb Haemost 120(4):702–713. https://doi.org/10.1055/s-0040-1708481
doi: 10.1055/s-0040-1708481
pubmed: 32289865
Agnelli G, Becattini C, Meyer G, Muñoz A, Huisman MV, Connors JM et al (2020) Caravaggio Investigators. Apixaban for the treatment of venous thromboembolism associated with cancer. N Engl J Med 382(17):1599–1607. https://doi.org/10.1056/NEJMoa1915103
doi: 10.1056/NEJMoa1915103
pubmed: 32223112
Young AM, Marshall A, Thirlwall J, Chapman O, Lokare A, Hill C et al (2018) 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 36(20):2017–2023. https://doi.org/10.1200/JCO.2018.78.8034
doi: 10.1200/JCO.2018.78.8034
pubmed: 29746227
Raskob GE, van Es N, Verhamme P, Carrier M, Di Nisio M, Garcia D et al (2018) Hokusai VTE Cancer Investigators. Edoxaban for the treatment of cancer-associated venous thromboembolism. N Engl J Med 378(7):615–624. https://doi.org/10.1056/NEJMoa1711948
doi: 10.1056/NEJMoa1711948
pubmed: 29231094
Farge D, Frere C, Connors JM, Ay C, Khorana AA, Munoz A, International Initiative on Thrombosis and Cancer (ITAC) advisory panel et al (2019) International clinical practice guidelines for the treatment and prophylaxis of venous thromboembolism in patients with cancer. Lancet Oncol 20(10):e566–e581. https://doi.org/10.1016/S1470-2045(19)30336-5
doi: 10.1016/S1470-2045(19)30336-5
pubmed: 31492632
Key NS, Khorana AA, Kuderer NM, Bohlke K, Lee AYY, Arcelus JI et al (2020) Venous thromboembolism prophylaxis and treatment in patients with cancer: ASCO clinical practice guideline update. J Clin Oncol 38(5):496–520. https://doi.org/10.1200/JCO.19.01461
doi: 10.1200/JCO.19.01461
pubmed: 31381464
Castellucci LA, Cameron C, Le Gal G, Rodger MA, Coyle D, Wells PS et al (2013) Efficacy and safety outcomes of oral anticoagulants and antiplatelet drugs in the secondary prevention of venous thromboembolism: systematic review and network meta-analysis. BMJ 30(347):f5133. https://doi.org/10.1136/bmj.f5133
doi: 10.1136/bmj.f5133
Bikdeli B, Zahedi TF, Sadeghipour P, Talasaz AH, Fanikos J, Lippi G et al (2022) Efficacy and safety considerations with dose-reduced direct oral anticoagulants: a review. JAMA Cardiol 7(7):747–759. https://doi.org/10.1001/jamacardio.2022.1292 . Erratum in: JAMA Cardiol. 2022 Jul 1;7(7):776
doi: 10.1001/jamacardio.2022.1292
pubmed: 35648414
Agnelli G, Buller HR, Cohen A, Curto M, Gallus AS, Johnson M et al (2013) AMPLIFY-EXT Investigators. Apixaban for extended treatment of venous thromboembolism. N Engl J Med 368(8):699–708. https://doi.org/10.1056/NEJMoa1207541
doi: 10.1056/NEJMoa1207541
pubmed: 23216615
Weitz JI, Lensing AWA, Prins MH, Bauersachs R, Beyer-Westendorf J, Bounameaux H et al (2017) EINSTEIN CHOICE Investigators. Rivaroxaban or aspirin for extended treatment of venous thromboembolism. N Engl J Med 376(13):1211–1222. https://doi.org/10.1056/NEJMoa1700518
doi: 10.1056/NEJMoa1700518
pubmed: 28316279
De Stefano V, Sorà F, Rossi E, Chiusolo P, Laurenti L, Fianchi L et al (2005) The risk of thrombosis in patients with acute leukemia: occurrence of thrombosis at diagnosis and during treatment. J Thromb Haemost 3(9):1985–1992. https://doi.org/10.1111/j.1538-7836.2005.01467.x
doi: 10.1111/j.1538-7836.2005.01467.x
pubmed: 16102104
Annibali O, Napolitano M, Avvisati G, Siragusa S (2018) Incidence of venous thromboembolism and use of anticoagulation in hematological malignancies: critical review of the literature. Crit Rev Oncol Hematol 124:41–50
doi: 10.1016/j.critrevonc.2018.02.003
pubmed: 29548485
Grace RF, Dahlberg SE, Neuberg D, Sallan SE, Connors JM, Neufeld EJ et al (2011) The frequency and management of asparaginase-related thrombosis in paediatric and adult patients with acute lymphoblastic leukaemia treated on Dana-Farber Cancer Institute consortium protocols. Br J Haematol 152(4):452–459. https://doi.org/10.1111/j.1365-2141.2010.08524.x
doi: 10.1111/j.1365-2141.2010.08524.x
pubmed: 21210774
pmcid: 5763913
Yokoyama K, Murata M, Ikeda Y, Okamoto S (2012) Incidence and risk factors for developing venous thromboembolism in Japanese with diffuse large b-cell lymphoma. Thromb Res 130(1):7–11. https://doi.org/10.1016/j.thromres.2011.09.022
doi: 10.1016/j.thromres.2011.09.022
pubmed: 22000981
Kristinsson SY, Fears TR, Gridley G, Turesson I, Mellqvist UH, Björkholm M et al (2008) Deep vein thrombosis after monoclonal gammopathy of undetermined significance and multiple myeloma. Blood 112(9):3582–3586. https://doi.org/10.1182/blood-2008-04-151076
doi: 10.1182/blood-2008-04-151076
pubmed: 18559977
pmcid: 2572787
Carrier M, Le Gal G, Tay J, Wu C, Lee AY (2011) Rates of venous thromboembolism in multiple myeloma patients undergoing immunomodulatory therapy with thalidomide or lenalidomide: a systematic review and meta-analysis. J Thromb Haemost 9(4):653–663. https://doi.org/10.1111/j.1538-7836.2011.04215.x
doi: 10.1111/j.1538-7836.2011.04215.x
pubmed: 21255254
Ku GH, White RH, Chew HK, Harvey DJ, Zhou H, Wun T (2009) Venous thromboembolism in patients with acute leukemia: incidence, risk factors, and effect on survival. Blood 113(17):3911–3917. https://doi.org/10.1182/blood-2008-08-175745
doi: 10.1182/blood-2008-08-175745
pubmed: 19088376
pmcid: 2673120
Hunault-Berger M, Chevallier P, Delain M, Bulabois CE, Bologna S, Bernard M et al (2008) GOELAMS (Groupe Ouest-Est des Leucémies Aiguës et Maladies du Sang). Changes in antithrombin and fibrinogen levels during induction chemotherapy with L-asparaginase in adult patients with acute lymphoblastic leukemia or lymphoblastic lymphoma. Use of supportive coagulation therapy and clinical outcome: the CAPELAL study. Haematologica 93(10):1488–1494
doi: 10.3324/haematol.12948
pubmed: 18728028
Napolitano M, Saccullo G, Marietta M, Carpenedo M, Castaman G, Cerchiara E, Chistolini A, Contino L, De Stefano V, Falanga A, Federici AB, Rossi E, Santoro R, Siragusa S (2019) Gruppo Italiano Malattie EMatologiche dell’Adulto (GIMEMA) Working Party on Thrombosis and Hemostasis; Gruppo Italiano Malattie Ematologiche dell’Adulto (GIMEMA) Working Party on Thrombosis and Haemostasis. Platelet cut-off for anticoagulant therapy in thrombocytopenic patients with blood cancer and venous thromboembolism: an expert consensus. Blood Transfus 17(3):171–180
pubmed: 30418130
pmcid: 6596377
Napolitano M, Valore L, Malato A, Saccullo G, Vetro C, Mitra ME, Fabbiano F, Mannina D, Casuccio A, Lucchesi A, Del Principe MI, Candoni A, Di Raimondo F, Siragusa S (2016) Management of venous thromboembolism in patients with acute leukemia at high bleeding risk: a multi-center study. Leuk Lymphoma 57(1):116–119
doi: 10.3109/10428194.2015.1046864
pubmed: 25944377
Campbell PM, Ippoliti C, Parmar S (2017) Safety of anticoagulation in thrombocytopenic patients with hematologic malignancies: a case series. J Oncol Pharm Pract 23(3):220–225. https://doi.org/10.1177/1078155216631407
doi: 10.1177/1078155216631407
pubmed: 26854266
Kaatz S, Ahmad D, Spyropoulos AC, Schulman S, Subcommittee on Control of Anticoagulation (2015) 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 13(11):2119–2126. https://doi.org/10.1111/jth.13140
doi: 10.1111/jth.13140
pubmed: 26764429
Schulman S, Kearon C (2005) 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 3(4):692–694. https://doi.org/10.1111/j.1538-7836.2005.01204.x
doi: 10.1111/j.1538-7836.2005.01204.x
pubmed: 15842354
Sakamoto J, Yamashita Y, Morimoto T, Amano H, Takase T, Hiramori S et al (2019) COMMAND VTE Registry Investigators. Cancer-associated venous thromboembolism in the real world - from the COMMAND VTE Registry. Circ J 83(11):2271–2281. https://doi.org/10.1253/circj.CJ-19-0515
doi: 10.1253/circj.CJ-19-0515
pubmed: 31548438
Marshall A, Levine M, Hill C, Hale D, Thirlwall J, Wilkie V et al (2020) Treatment of cancer-associated venous thromboembolism: 12-month outcomes of the placebo versus rivaroxaban randomization of the SELECT-D Trial (SELECT-D: 12m). J Thromb Haemost 18(4):905–915. https://doi.org/10.1111/jth.14752
doi: 10.1111/jth.14752
pubmed: 31995662
Di Nisio M, van Es N, Carrier M, Wang TF, Garcia D, Segers A et al (2019) Extended treatment with edoxaban in cancer patients with venous thromboembolism: a post-hoc analysis of the Hokusai-VTE Cancer study. J Thromb Haemost 17(11):1866–1874. https://doi.org/10.1111/jth.14561
doi: 10.1111/jth.14561
pubmed: 31271705
Napolitano M, Saccullo G, Malato A, Sprini D, Ageno W, Imberti D et al (2014) Optimal duration of low molecular weight heparin for the treatment of cancer-related deep vein thrombosis: the Cancer-DACUS Study. J Clin Oncol 32(32):3607–3612. https://doi.org/10.1200/JCO.2013.51.7433
doi: 10.1200/JCO.2013.51.7433
pubmed: 25267738
Jara-Palomares L, Solier-Lopez A, Elias-Hernandez T, Asensio-Cruz M, Blasco-Esquivias I, Marin-Barrera L et al (2017) Tinzaparin in cancer associated thrombosis beyond 6months: TiCAT study. Thromb Res 157:90–96. https://doi.org/10.1016/j.thromres.2017.07.004
doi: 10.1016/j.thromres.2017.07.004
pubmed: 28719850
Francis CW, Kessler CM, Goldhaber SZ, Kovacs MJ, Monreal M, Huisman MV et al (2015) Treatment of venous thromboembolism in cancer patients with dalteparin for up to 12 months: the DALTECAN Study. J Thromb Haemost 13(6):1028–1035. https://doi.org/10.1111/jth.12923
doi: 10.1111/jth.12923
pubmed: 25827941
Lyman GH, Carrier M, Ay C, Di Nisio M, Hicks LK, Khorana AA et al (2021) American Society of Hematology 2021 guidelines for management of venous thromboembolism: prevention and treatment in patients with cancer. Blood Adv 5(4):927–974. https://doi.org/10.1182/bloodadvances.2020003442 . Erratum in: Blood Adv. 2021 Apr 13;5(7):1953
doi: 10.1182/bloodadvances.2020003442
pubmed: 33570602
pmcid: 7903232
Serrao A, Assanto GM, Mormile R, Brescini M, Santoro C, Chistolini A (2022) Secondary prophylaxis of venous thromboembolism with direct oral anticoagulants: comparison between patients with major congenital thrombophilia versus non-thrombophilic patients. Intern Emerg Med 17(4):1081–1085. https://doi.org/10.1007/s11739-021-02917-3
doi: 10.1007/s11739-021-02917-3
pubmed: 35018544
Vasanthamohan L, Boonyawat K, Chai-Adisaksopha C, Crowther M (2018) Reduced-dose direct oral anticoagulants in the extended treatment of venous thromboembolism: a systematic review and meta-analysis. J Thromb Haemost 16(7):1288–1295. https://doi.org/10.1111/jth.14156 . Erratum in: J Thromb Haemost. 2021 Sep;19(9):2365-2366
doi: 10.1111/jth.14156
pubmed: 29772108
Barca-Hernando M, Marin-Romero S, Jara-Palomares L (2022) Low-dose apixaban in extended treatment of cancer-associated thrombosis: less is more? J Thromb Haemost 20(5):1070–1072. https://doi.org/10.1111/jth.15685
doi: 10.1111/jth.15685
pubmed: 35445577
Serrao A, Assanto GM, Malfona F, Chavez OG, Chistolini A (2022) “Low dose apixaban as secondary prophylaxis of venous thromboembolism in cancer patients-30 months follow-up”: comment from Serrao et al. J Thromb Haemost 20(8):1935–1937. https://doi.org/10.1111/jth.15775
doi: 10.1111/jth.15775
pubmed: 35859279
Larsen TL, Garresori H, Brekke J, Enden T, Frøen H, Jacobsen EM et al (2022) Low dose apixaban as secondary prophylaxis of venous thromboembolism in cancer patients - 30 months follow-up. J Thromb Haemost 20(5):1166–1181. https://doi.org/10.1111/jth.15666
doi: 10.1111/jth.15666
pubmed: 35114046