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Outcomes With Edoxaban Versus Warfarin in Patients With Previous Cerebrovascular Events Findings From ENGAGE AF-TIMI 48 (Effective Anticoagulation With Factor Xa Next Generation in Atrial Fibrillation-Thrombolysis in Myocardial Infarction 48)

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Rost, Natalia S.Giugliano, Robert P.Ruff, Christian T.Murphy, Sabina A.Crompton, Andrea E.Norden, Andrew D.Silverman, ScottSinghal, Aneesh B.Nicolau, Jose C.SomaRaju, BhupathiMercuri, Michele F.Antman, Elliott M.Braunwald, EugeneENGAGE 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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Issue Date
Aug-2016
Publisher
Lippincott Williams & Wilkins Ltd.
Keywords
atrial fibrillation; clinical trial; hemorrhage; risk factors; stroke
Citation
Stroke, v.47, no.8, pp 2075 - 2082
Pages
8
Indexed
SCI
SCIE
SCOPUS
Journal Title
Stroke
Volume
47
Number
8
Start Page
2075
End Page
2082
URI
https://scholarworks.korea.ac.kr/kumedicine/handle/2020.sw.kumedicine/52274
DOI
10.1161/STROKEAHA.116.013540
ISSN
0039-2499
1524-4628
Abstract
Background and Purpose— Patients with atrial fibrillation and previous ischemic stroke (IS)/transient ischemic attack (TIA) are at high risk of recurrent cerebrovascular events despite anticoagulation. In this prespecified subgroup analysis, we compared warfarin with edoxaban in patients with versus without previous IS/TIA. Methods— ENGAGE AF-TIMI 48 (Effective Anticoagulation With Factor Xa Next Generation in Atrial Fibrillation-Thrombolysis in Myocardial Infarction 48) was a double-blind trial of 21 105 patients with atrial fibrillation randomized to warfarin (international normalized ratio, 2.0–3.0; median time-in-therapeutic range, 68.4%) versus once-daily edoxaban (higher-dose edoxaban regimen [HDER], 60/30 mg; lower-dose edoxaban regimen, 30/15 mg) with 2.8-year median follow-up. Primary end points included all stroke/systemic embolic events (efficacy) and major bleeding (safety). Because only HDER is approved, we focused on the comparison of HDER versus warfarin. Results— Of 5973 (28.3%) patients with previous IS/TIA, 67% had CHADS2 (congestive heart failure, hypertension, age, diabetes, prior stroke/transient ischemic attack) >3 and 36% were ≥75 years. Compared with 15 132 without previous IS/TIA, patients with previous IS/TIA were at higher risk of both thromboembolism and bleeding (stroke/systemic embolic events 2.83% versus 1.42% per year; P<0.001; major bleeding 3.03% versus 2.64% per year; P<0.001; intracranial hemorrhage, 0.70% versus 0.40% per year; P<0.001). Among patients with previous IS/TIA, annualized intracranial hemorrhage rates were lower with HDER than with warfarin (0.62% versus 1.09%; absolute risk difference, 47 [8–85] per 10 000 patient-years; hazard ratio, 0.57; 95% confidence interval, 0.36–0.92; P=0.02). No treatment subgroup interactions were found for primary efficacy (P=0.86) or for intracranial hemorrhage (P=0.28). Conclusions— Patients with atrial fibrillation with previous IS/TIA are at high risk of recurrent thromboembolism and bleeding. HDER is at least as effective and is safer than warfarin, regardless of the presence or the absence of previous IS or TIA. Clinical Trial Registration— URL: http://www.clinicaltrials.gov. Unique identifier: NCT00781391.
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Na, Jin Oh
Guro Hospital (Department of Cardiology, Guro Hospital)
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