1. Edoxaban for the treatment of cancer-associated venous thromboembolism
- Author
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Raskob, GE, van Es, N, Verhamme, P, Carrier, M, Di Nisio, M, Garcia, D, Grosso, MA, Kakkar, AK, Kovacs, MJ, Mercuri, MF, Meyer, G, Segers, A, Shi, M, Wang, TF, Yeo, E, Zhang, G, Zwicker, JI, Weitz, JI, Büller, HR, Beyer-Westendorf, J, Boda, Z, Chlumsky, Y, Gibbs, H, Kamphuizen, PW, Monreal, M, Ockleford, P, Pabinger-Fasching, I, Sinnaeve, P, Beenen, L, Gerdes, V, Laleman, W, Larrey, D, van Mechelen, R, Roos, Y, Scheerder, M, Slagboom, T, Thijs, V, Eikelboom, JW, Crowther, M, Roberts, RS, Vanassche, T, Vandenbriele, C, Debaveye, B, Dani, V, Schwocho, L, Duggal, A, Baker, R, Carroll, P, Chan, N, Coughlin, P, Crispin, P, Gallus, A, Hugman, A, Tran, H, Brodmann, M, Mathies, R, Rossmann, D, Deeren, D, Hainaut, P, Jochmans, K, Vercauter, P, Wautrecht, JC, Champion, P, Gross, P, Lee, A, Shivakumar, S, Tagalakis, V, Zed, E, Kovarova, K, Lastuvka, J, Matoska, P, Prosecky, R, Achkar, A, Aquilanti, S, Chatellain, P, Cony-Makhoul, P, Del Piano, F, Elias, A, Falvo, N, Ferrari, E, Mahé, I, Merle, P, Mismetti, P, Muron, T, Pernod, G, Quere, I, Schmidt, J, Stephan, D, Espinola-Klein, C, Horacek, T, Kröning, R, Oettler, W, Schellong, S, Schön, N, Zwemmrich, C, Farkas, K, Gurzo, M, Nyirati, G, Pecsvarady, Z, Riba, M, Becattini, C, Cattaneo, M, Falanga, A, Ghirarduzzi, A, Imberti, D, Lodigiani, C, Parisi, R, Porreca, E, Squizzato, A, Tassoni, MI, Villalta, S, Visonà, A, Beeker, A, Boersma, W, Brouwer, R, Dees, A, Huisman, M, Kuijer, P, Mairuhu, R, Meijer, K, Middeldorp, S, Otten, HM, van Marwijk-Kooy, M, van Wissen, S, Westerweel, P, Harper, P, Merriman, E, Ockelford, P, Royle, G, Smith, M, Cereto Castro, F, de Oña Navarrete, R, Font Puig, C, Gallardo Díaz, E, Garcia-Bragado Dalmau, F, Ruiz Artacho, P, Santamaria, A, Baumann Kreuziger, L, De Sancho, M, Gaddh, M, Metjian, A, Rojas Hernandez, CM, Shah, V, Smith, W, Wun, T, Xiang, Z, Raskob, G, van Es, N, Verhamme, P, Carrier, M, Di Nisio, M, Garcia, D, Grosso, M, Kakkar, A, Kovacs, M, Mercuri, M, Meyer, G, Segers, A, Shi, M, Wang, T, Yeo, E, Zhang, G, Zwicker, J, Weitz, J, Büller, H, Beyer-Westendorf, J, Boda, Z, Chlumsky, Y, Gibbs, H, Kamphuizen, P, Monreal, M, Ockleford, P, Pabinger-Fasching, I, Sinnaeve, P, Beenen, L, Gerdes, V, Laleman, W, Larrey, D, van Mechelen, R, Roos, Y, Scheerder, M, Slagboom, T, Thijs, V, Eikelboom, J, Crowther, M, Roberts, R, Vanassche, T, Vandenbriele, C, Debaveye, B, Dani, V, Schwocho, L, Duggal, A, Baker, R, Carroll, P, Chan, N, Coughlin, P, Crispin, P, Gallus, A, Hugman, A, Tran, H, Brodmann, M, Mathies, R, Rossmann, D, Deeren, D, Hainaut, P, Jochmans, K, Vercauter, P, Wautrecht, J, Champion, P, Gross, P, Lee, A, Shivakumar, S, Tagalakis, V, Zed, E, Kovarova, K, Lastuvka, J, Matoska, P, Prosecky, R, Achkar, A, Aquilanti, S, Chatellain, P, Cony-Makhoul, P, Del Piano, F, Elias, A, Falvo, N, Ferrari, E, Mahé, I, Merle, P, Mismetti, P, Muron, T, Pernod, G, Quere, I, Schmidt, J, Stephan, D, Espinola-Klein, C, Horacek, T, Kröning, R, Oettler, W, Schellong, S, Schön, N, Zwemmrich, C, Farkas, K, Gurzo, M, Nyirati, G, Pecsvarady, Z, Riba, M, Becattini, C, Cattaneo, M, Falanga, A, Ghirarduzzi, A, Imberti, D, Lodigiani, C, Parisi, R, Porreca, E, Squizzato, A, Tassoni, M, Villalta, S, Visonà, A, Beeker, A, Boersma, W, Brouwer, R, Dees, A, Huisman, M, Kuijer, P, Mairuhu, R, Meijer, K, Middeldorp, S, Otten, H, van Marwijk-Kooy, M, van Wissen, S, Westerweel, P, Harper, P, Merriman, E, Ockelford, P, Royle, G, Smith, M, Cereto Castro, F, de Oña Navarrete, R, Font Puig, C, Gallardo Díaz, E, Garcia-Bragado Dalmau, F, Ruiz Artacho, P, Santamaria, A, Baumann Kreuziger, L, De Sancho, M, Gaddh, M, Metjian, A, Rojas Hernandez, C, Shah, V, Smith, W, Wun, T, Xiang, Z, Graduate School, CCA - Cancer Treatment and Quality of Life, Vascular Medicine, ACS - Amsterdam Cardiovascular Sciences, ANS - Neurovascular Disorders, Radiology and Nuclear Medicine, Other Research, Other departments, Neurology, APH - Societal Participation & Health, APH - Quality of Care, Coronel Institute of Occupational Health, ARD - Amsterdam Reproduction and Development, AGEM - Amsterdam Gastroenterology Endocrinology Metabolism, ACS - Atherosclerosis & ischemic syndromes, ACS - Pulmonary hypertension & thrombosis, and ACS - Microcirculation
- Subjects
Adult ,Dalteparin ,Male ,Randomization ,Pyridines ,Hemorrhage ,Kaplan-Meier Estimate ,030204 cardiovascular system & hematology ,law.invention ,03 medical and health sciences ,chemistry.chemical_compound ,0302 clinical medicine ,Randomized controlled trial ,Recurrence ,law ,Edoxaban ,Neoplasms ,medicine ,Humans ,Aged ,Intention-to-treat analysis ,Heparin ,business.industry ,Standard treatment ,Low-Molecular-Weight ,Anticoagulants ,Cancer ,Follow-Up Studies ,Heparin, Low-Molecular-Weight ,Intention to Treat Analysis ,Middle Aged ,Thiazoles ,Venous Thromboembolism ,General Medicine ,medicine.disease ,Thrombosis ,chemistry ,030220 oncology & carcinogenesis ,Anesthesia ,Venous Thromboembolism, cancer, thrombosis ,business ,medicine.drug - Abstract
BACKGROUND Low-molecular-weight heparin is the standard treatment for cancer-associated venous thromboembolism. The role of treatment with direct oral anticoagulant agents is unclear. METHODS In this open-label, noninferiority trial, we randomly assigned patients with cancer who had acute symptomatic or incidental venous thromboembolism to receive either low-molecular-weight heparin for at least 5 days followed by oral edoxaban at a dose of 60 mg once daily (edoxaban group) or subcutaneous dalteparin at a dose of 200 IU per kilogram of body weight once daily for 1 month followed by dalteparin at a dose of 150 IU per kilogram once daily (dalteparin group). Treatment was given for at least 6 months and up to 12 months. The primary outcome was a composite of recurrent venous thromboembolism or major bleeding during the 12 months after randomization, regardless of treatment duration. RESULTS Of the 1050 patients who underwent randomization, 1046 were included in the modified intention-to-treat analysis. A primary-outcome event occurred in 67 of the 522 patients (12.8%) in the edoxaban group as compared with 71 of the 524 patients (13.5%) in the dalteparin group (hazard ratio, 0.97; 95% confidence interval [CI], 0.70 to 1.36; P = 0.006 for noninferiority; P = 0.87 for superiority). Recurrent venous thromboembolism occurred in 41 patients (7.9%) in the edoxaban group and in 59 patients (11.3%) in the dalteparin group (difference in risk, -3.4 percentage points; 95% CI, -7.0 to 0.2). Major bleeding occurred in 36 patients (6.9%) in the edoxaban group and in 21 patients (4.0%) in the dalteparin group (difference in risk, 2.9 percentage points; 95% CI, 0.1 to 5.6). CONCLUSIONS Oral edoxaban was noninferior to subcutaneous dalteparin with respect to the composite outcome of recurrent venous thromboembolism or major bleeding. The rate of recurrent venous thromboembolism was lower but the rate of major bleeding was higher with edoxaban than with dalteparin. (Funded by Daiichi Sankyo; Hokusai VTE Cancer ClinicalTrials. gov number, NCT02073682.)
- Published
- 2018