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Bleeding with Apixaban and Dalteparin in Patients with Cancer-Associated Venous Thromboembolism: Results from the Caravaggio StudyFunding This study (NCT03045406) was supported by Bristol-Myers Squibb-Pfizer Alliance. Bristol-Myers Squibb-Pfizer Alliance provided the study drugs. The corresponding author has full access to all the data in the study.
Background Direct oral anticoagulants are recommended for the treatment of cancer-associated thrombosis (CAT) as an alternative to low-molecular-weight heparin (LMWH), but an increased bleeding risk in patients with gastrointestinal cancer was reported. The Caravaggio study compared apixaban and dalteparin for the treatment of patients with CAT. Here we describe sites of bleeding, associated cancer sites, clinical presentation, and course of major bleeding in patients included in the Caravaggio study.
Methods The Caravaggio study was a multinational, randomized, open-label, noninferiority study. Bleeding events and the severity of major bleedings were adjudicated by a committee unaware of treatment allocation using predefined criteria; for the purpose of this analysis, data were analyzed in the safety population.
Results Major bleeding occurred in 22 of 576 patients on apixaban (3.8%) and in 23 of 579 patients on dalteparin (4.0%). The sites of major bleeding and their distribution according to the type of cancer were similar between the two treatment groups. Major bleeding occurred in nine patients with gastrointestinal cancer in each treatment group. The clinical presentation of major bleeding was severe or fatal in 6 patients on apixaban and in 5 patients on dalteparin, while the clinical course was severe in 5 patients on apixaban and in 7 patients on dalteparin.
Conclusion Apixaban is a safe alternative to LMWH for the treatment in patients with CAT. No excess in gastrointestinal bleeding was observed in patients who received apixaban, including those with gastrointestinal cancer.
W.A., M.C.V., C.B, and G.A. contributed to the conception of the work; A.C., M.H., R.B., and G.G. contributed to the interpretation of data for the work; W.A., M.C.V., C.B., and G.A. participated in drafting the manuscript; A.C., M.H., R.B., and G.G. critically reviewed the manuscript for important intellectual content; W.A., M.C.V., A.C., M.H., R.B., G.G., C.B., and G.A. approved the final submitted version to be published; W.A., M.C.V., A.C., M.H., R.B., G.G., C.B., and G.A. agreed to be accountable for all aspects of the work in ensuring that questions related to the accuracy or integrity of any part of the work are appropriately investigated and resolved.
Received: 12 August 2020
Accepted: 23 September 2020
Article published online:
17 November 2020
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- 1 Konstantinides SV, Meyer G, Becattini C. et al; ESC Scientific Document Group. 2019 ESC guidelines for the diagnosis and management of acute pulmonary embolism developed in collaboration with the European Respiratory Society (ERS). Eur Heart J 2020; 41 (04) 543-603
- 2 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
- 3 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
- 4 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
- 5 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
- 6 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
- 7 Streiff MB, Holmstrom B, Angelini D. et al. NCCN guidelines insights: cancer-associated venous thromboembolic disease, version 2.2018. J Natl Compr Canc Netw 2018; 16 (11) 1289-1303
- 8 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
- 9 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
- 10 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
- 11 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
- 12 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
- 13 Carrier M, Prandoni P. Controversies in the management of cancer-associated thrombosis. Expert Rev Hematol 2017; 10 (01) 15-22
- 14 Kearon C, Akl EA, Ornelas J. et al. Antithrombotic therapy for VTE disease. Chest 2016; 149 (02) 315-352
- 15 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
- 16 Ageno W, Haas S, Weitz JI. et al; GARFIELD-VTE investigators. Characteristics and management of patients with venous thromboembolism: the GARFIELD-VTE registry. Thromb Haemost 2019; 119 (02) 319-327
- 17 van Es N, Coppens M, Schulman S, Middeldorp S, Büller HR. Direct oral anticoagulants compared with vitamin K antagonists for acute venous thromboembolism: evidence from phase 3 trials. Blood 2014; 124 (12) 1968-1975
- 18 Ruff CT, Giugliano RP, Braunwald E. et al. Comparison of the efficacy and safety of new oral anticoagulants with warfarin in patients with atrial fibrillation: a meta-analysis of randomised trials. Lancet 2014; 383 (9921): 955-962
- 19 Martinelli I, Lensing AWA, Middeldorp S. et al. Recurrent venous thromboembolism and abnormal uterine bleeding with anticoagulant and hormone therapy use. Blood 2016; 127 (11) 1417-1425
- 20 Granger CB, Alexander JH, McMurray JJV. et al; ARISTOTLE Committees and Investigators. Apixaban versus warfarin in patients with atrial fibrillation. N Engl J Med 2011; 365 (11) 981-992
- 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 Carmona-Bayonas A, Gómez D, Martínez de Castro E. et al. A snapshot of cancer-associated thromboembolic disease in 2018-2019: first data from the TESEO prospective registry. Eur J Intern Med 2020; 78: 41-49