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Edoxaban versus Warfarin in Patients with Atrial Fibrillation

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Giugliano, Robert P.Ruff, Christian T.Braunwald, EugeneMurphy, Sabina A.Wiviott, Stephen D.Halperin, Jonathan L.Waldo, Albert L.Ezekowitz, Michael D.Weitz, Jeffrey I.Spinar, JindrichRuzyllo, WitoldRuda, MikhailKoretsune, YukihiroBetcher, JoshuaShi, MinggaoGrip, Laura T.Patel, Shirali P.Patel, IndravadanHanyok, James J.Mercuri, MicheleAntman, Elliott M.ENGAGE AF-TIMI 48 InvestigatorsVogelmann, O.Gonzalez, C.Ahuad Guerrero, R.Rodriguez, M.Albisu, J.Rosales, E.Allall, O.Reguero, M.Alvarez, C.Garcia, M.Ameriso, S.Ameriso, P.Amuchastegui, M.Caceres, M.Beloscar, J.Petrucci, J.Berli, M.Budassi, N.Valle, M.Bustamante Labarta, G.Saravia, M.Caccavo, A.Fracaro, V.Cartasegna, L.Novas, V.Caruso, O.Saa Zarandon, R.Colombo, H.Morandini, M.Cuello, J.Rosell, M.Cuneo, C.Bocanera, M.D'Amico, A.Cendali, G.Dran, R.Moreno, V.Estol, C.Davolos, M.Facello, A.Facello, M.Falu, E.Iriarte, M.Femenia, F.Arrieta, M.Fuselli, J.Zanotti, A.Gant Lopez, J.Meiller, F.Garcia Duran, R.Perlo, D.Garrido, M.Ceirano, C.Giacomi, G.Eden, M.Giannaula, R.Huerta, M.Goicoechea, R.von Wulffen, M.Hominal, M.Bianchini, M.Jure, H.Jure, D.Kevorkian, R.Monaco, F.Lanternier, G.Belcuore, M.Liniado, G.Iglesias, M.Litvak, B.Nigro, A.Llanos, J.Vignau, S.Lorente, C.Shatsky, K.Lotti, J.Raimondi, G.Mackinnon, I.Carne, M.Manuale, O.Calderon, M.Marino, J.Funes, I.Muntaner, J.Gandur, H.Nul, D.Verdini, E.Piskorz, D.Tommasi, A.Povedano, G.Casares, E.Pozzer, D.Fernandez, E.Prado, A.Venturini, C.Ramos, H.Navarrete, S.Rodriguez, M.Alvarez, M.Sanchez, A.Bowen, L.Sanjurjo, M.Codutti, O.Saravia Toledo, S.Formoso, I.Schmidberg, J.Goloboulicz, A.Schygiel, P.Buzzetti, C.Severino, P.Morara, P.Sosa Liprandi, M.Teves, M.Vico, M.Morell, Y.Anderson, C.Anderson, C.Paraskevaidis, T.Arstall, M.Hoffmann, B.Colquhoun, D.Price-Smith, S.Crimmins, D.Slattery, A.Dart, A.Kay, S.Davis, S.Silver, G.Flecknoe-Brown, S.Roberts, J.Gates, P.Jones, S.Lehman, R.Morrison, H.McKeirnan, M.Li, J.Paul, V.Batta, C.Purnell, P.Perrett, L.Szto, G.O'Shea, V.Capiau, L.Banaeian, F.De Bleecker, J.de Koning, K.De Tollenaere, M.De Bruyne, L.Desfontaines, P.Tincani, G.Heidbuchel, H.Meeusen, K.Herzet, J.Malmendier, D.Mairesse, G.Raepers, M.Parque, J.Clinckemaille, N.Scavee, C.Huyberechts, D.Stockman, D.Jacobs, C.Vandekerckhove, Y.Derycker, K.Vanwelden, J.van Welden, J.Vervoort, G.Mestdagh, I.Vrolix, M.Beerts, C.Wollaert, B.Denie, D.Vincenzo de Paola, A. 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GonzalezVemireddy, D.Cardoza, T.Verma, S.Parsons, T.Vicari, R.Warren, K.Vijay, N.Washam, M.Vossler, M.Kilcup, S.Walsh, R.Renaud, K.Ward, S.Locklear, T.Waxman, F.Sanchez, G.Weiss, R.St Laurent, B.Westcott, J.Truva, C.Williams, D.Gibson, C.Williams, R.Dowling, C.Willis, J.VonGerichten, S.Wood, K.Capasso-Gulve, E.Worley, S.Pointer, S.Yarows, S.Sheehan, T.Yasin, M.Preston, S.Yi, J.Dongas, B.Yousuf, K.Fisher, M.Zakhary, B.Curtis, S.Zeig, S.Mason, T.Zellner, C.Harden, M.Roper, E.Waseem, M.Grammer, M.
Issue Date
Nov-2013
Publisher
Massachusetts Medical Society
Citation
New England Journal of Medicine, v.369, no.22, pp 2093 - 2104
Pages
12
Indexed
SCI
SCIE
SCOPUS
Journal Title
New England Journal of Medicine
Volume
369
Number
22
Start Page
2093
End Page
2104
URI
https://scholarworks.korea.ac.kr/kumedicine/handle/2020.sw.kumedicine/52272
DOI
10.1056/NEJMoa1310907
ISSN
0028-4793
1533-4406
Abstract
BACKGROUND Edoxaban is a direct oral factor Xa inhibitor with proven antithrombotic effects. The long-term efficacy and safety of edoxaban as compared with warfarin in patients with atrial fibrillation is not known. METHODS We conducted a randomized, double-blind, double-dummy trial comparing two once-daily regimens of edoxaban with warfarin in 21,105 patients with moderate-to-high-risk atrial fibrillation (median follow-up, 2.8 years). The primary efficacy end point was stroke or systemic embolism. Each edoxaban regimen was tested for noninferiority to warfarin during the treatment period. The principal safety end point was major bleeding. RESULTS The annualized rate of the primary end point during treatment was 1.50% with warfarin (median time in the therapeutic range, 68.4%), as compared with 1.18% with high-dose edoxaban (hazard ratio, 0.79; 97.5% confidence interval [CI], 0.63 to 0.99; P<0.001 for noninferiority) and 1.61% with low-dose edoxaban (hazard ratio, 1.07; 97.5% CI, 0.87 to 1.31; P=0.005 for noninferiority). In the intention-to-treat analysis, there was a trend favoring high-dose edoxaban versus warfarin (hazard ratio, 0.87; 97.5% CI, 0.73 to 1.04; P=0.08) and an unfavorable trend with low-dose edoxaban versus warfarin (hazard ratio, 1.13; 97.5% CI, 0.96 to 1.34; P=0.10). The annualized rate of major bleeding was 3.43% with warfarin versus 2.75% with high-dose edoxaban (hazard ratio, 0.80; 95% CI, 0.71 to 0.91; P<0.001) and 1.61% with low-dose edoxaban (hazard ratio, 0.47; 95% CI, 0.41 to 0.55; P<0.001). The corresponding annualized rates of death from cardiovascular causes were 3.17% versus 2.74% (hazard ratio, 0.86; 95% CI, 0.77 to 0.97; P=0.01), and 2.71% (hazard ratio, 0.85; 95% CI, 0.76 to 0.96; P=0.008), and the corresponding rates of the key secondary end point (a composite of stroke, systemic embolism, or death from cardiovascular causes) were 4.43% versus 3.85% (hazard ratio, 0.87; 95% CI, 0.78 to 0.96; P=0.005), and 4.23% (hazard ratio, 0.95; 95% CI, 0.86 to 1.05; P=0.32). CONCLUSIONS Both once-daily regimens of edoxaban were noninferior to warfarin with respect to the prevention of stroke or systemic embolism and were associated with significantly lower rates of bleeding and death from cardiovascular causes.
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Guro Hospital (Department of Cardiology, Guro Hospital)
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