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N Engl J Med. 2018 Feb 15;378(7):615-624. doi: 10.1056/NEJMoa1711948. Epub 2017 Dec 12.

Edoxaban for the Treatment of Cancer-Associated Venous Thromboembolism.

Collaborators (127)

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.

Author information

1
From the University of Oklahoma Health Sciences Center, College of Public Health, Oklahoma City (G.E.R.); the Department of Vascular Medicine, Academic Medical Center, University of Amsterdam (N.E., H.R.B.), and ITREAS, Academic Research Organization (A.S.) - both in Amsterdam; the Department of Vascular Medicine and Hemostasis, University Hospitals Leuven, Leuven, Belgium (P.V.); Ottawa Hospital Research Institute, Ottawa (M.C.), London Health Sciences Centre-Victoria Hospital, London, ON (M.J.K.), University Health Network, University of Toronto, Toronto (E.Y.), and McMaster University and the Thrombosis and Atherosclerosis Research Institute, Hamilton, ON (J.I.W.) - all in Canada; the Department of Medicine and Aging Sciences, University G. D'Annunzio, Chieti, Italy (M.D.N.); the Department of Medicine, Division of Hematology, University of Washington, Seattle (D.G.); Daiichi Sankyo Pharma Development, Basking Ridge, NJ (M.A.G., M.F.M., M.S., G.Z.); Thrombosis Research Institute and University College London, London (A.K.K.); the Department of Respiratory Disease, Hôpital Européen Georges-Pompidou, Assistance Publique-Hôpitaux de Paris, Paris (G.M.); the Department of Internal Medicine, Division of Hematology, Ohio State University Wexner Medical Center, Columbus (T.-F.W.); and Beth Israel Deaconess Medical Center, Harvard Medical School, Boston (J.I.Z.).

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 .).

PMID:
29231094
DOI:
10.1056/NEJMoa1711948
[Indexed for MEDLINE]
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