title: Stroke and Mortality Risk in Patients With Various Patterns of Atrial Fibrillation: Results From the ENGAGE AF-TIMI 48 Trial (Effective Anticoagulation With Factor Xa Next Generation in Atrial Fibrillation-Thrombolysis in Myocardial Infarction 48).
abstract: Whether the pattern of atrial fibrillation (AF) modifies the risk/benefit of anticoagulation is controversial. In ENGAGE AF-TIMI 48 trial (Effective Anticoagulation with Factor Xa Next Generation in Atrial Fibrillation-Thrombolysis in Myocardial Infarction 48), the factor Xa inhibitor edoxaban was noninferior to warfarin in preventing stroke or systemic embolic events and significantly reduced bleeding and cardiovascular mortality. However, detailed analyses by AF pattern have not been reported.
  
  
  
  The 21 105 patients were categorized as having paroxysmal (<7 days duration), persistent (≥7 days but <1 year), or permanent (≥1 year or failed cardioversion) AF patterns at randomization. Efficacy and safety outcomes were evaluated during the 2.8 years median follow-up and compared by AF pattern. The primary end point of stroke/systemic embolic event was lower in those patients with paroxysmal AF (1.49%/year), compared with persistent (1.83%/year; P-adj =0.015) and permanent AF (1.95%/year; P-adj =0.004). Overall, all-cause mortality also was lower with paroxysmal (3.0%/year) compared with persistent (4.4%/year; P-adj <0.001) and permanent AF (4.4%/year; P-adj <0.001). Annualized major bleeding rates were similar across AF patterns (2.86% versus 2.65% versus 2.73%). There was no effect modification by treatment assignment.
  
  
  
  In ENGAGE AF-TIMI 48 trial, patients with paroxysmal AF suffered fewer thromboembolic events and deaths compared with those with persistent and permanent AF. The efficacy and safety profile of edoxaban as compared with warfarin was consistent across the 3 patterns of AF.
  
  
  
  URL: http://www.clinicaltrials.gov. Unique identifier: NCT00781391.
authors.affiliation: From the Department of Medicine, UTSouthwestern Medical Center, Dallas, TX (M.S.L.); TIMI Study Group, Brigham and Women's Hospital, Boston, MA (R.P.G., C.T.R., B.M.S., A.E.C., S.A.M., E.M.A., E.B.); Department of Medicine, University of Oulu, Finland (H.H.); Oulu University Hospital, Finland (H.H.); Heart and Health Foundation of Turkey, Ankara (A.O.); Daiichi-Sankyo Pharma Development, Munich, Germany (H.L.); and Daiichi-Sankyo Pharma Development, Edison, NJ (M.F.M.). mark.link@UTSouthwestern.edu.
authors.forename: Mark S
authors.initials: MS
authors.lastname: Link
authors.affiliation: From the Department of Medicine, UTSouthwestern Medical Center, Dallas, TX (M.S.L.); TIMI Study Group, Brigham and Women's Hospital, Boston, MA (R.P.G., C.T.R., B.M.S., A.E.C., S.A.M., E.M.A., E.B.); Department of Medicine, University of Oulu, Finland (H.H.); Oulu University Hospital, Finland (H.H.); Heart and Health Foundation of Turkey, Ankara (A.O.); Daiichi-Sankyo Pharma Development, Munich, Germany (H.L.); and Daiichi-Sankyo Pharma Development, Edison, NJ (M.F.M.).
authors.forename: Robert P
authors.initials: RP
authors.lastname: Giugliano
authors.affiliation: From the Department of Medicine, UTSouthwestern Medical Center, Dallas, TX (M.S.L.); TIMI Study Group, Brigham and Women's Hospital, Boston, MA (R.P.G., C.T.R., B.M.S., A.E.C., S.A.M., E.M.A., E.B.); Department of Medicine, University of Oulu, Finland (H.H.); Oulu University Hospital, Finland (H.H.); Heart and Health Foundation of Turkey, Ankara (A.O.); Daiichi-Sankyo Pharma Development, Munich, Germany (H.L.); and Daiichi-Sankyo Pharma Development, Edison, NJ (M.F.M.).
authors.forename: Christian T
authors.initials: CT
authors.lastname: Ruff
authors.affiliation: From the Department of Medicine, UTSouthwestern Medical Center, Dallas, TX (M.S.L.); TIMI Study Group, Brigham and Women's Hospital, Boston, MA (R.P.G., C.T.R., B.M.S., A.E.C., S.A.M., E.M.A., E.B.); Department of Medicine, University of Oulu, Finland (H.H.); Oulu University Hospital, Finland (H.H.); Heart and Health Foundation of Turkey, Ankara (A.O.); Daiichi-Sankyo Pharma Development, Munich, Germany (H.L.); and Daiichi-Sankyo Pharma Development, Edison, NJ (M.F.M.).
authors.forename: Benjamin M
authors.initials: BM
authors.lastname: Scirica
authors.affiliation: From the Department of Medicine, UTSouthwestern Medical Center, Dallas, TX (M.S.L.); TIMI Study Group, Brigham and Women's Hospital, Boston, MA (R.P.G., C.T.R., B.M.S., A.E.C., S.A.M., E.M.A., E.B.); Department of Medicine, University of Oulu, Finland (H.H.); Oulu University Hospital, Finland (H.H.); Heart and Health Foundation of Turkey, Ankara (A.O.); Daiichi-Sankyo Pharma Development, Munich, Germany (H.L.); and Daiichi-Sankyo Pharma Development, Edison, NJ (M.F.M.).
authors.forename: Heikke
authors.initials: H
authors.lastname: Huikuri
authors.affiliation: From the Department of Medicine, UTSouthwestern Medical Center, Dallas, TX (M.S.L.); TIMI Study Group, Brigham and Women's Hospital, Boston, MA (R.P.G., C.T.R., B.M.S., A.E.C., S.A.M., E.M.A., E.B.); Department of Medicine, University of Oulu, Finland (H.H.); Oulu University Hospital, Finland (H.H.); Heart and Health Foundation of Turkey, Ankara (A.O.); Daiichi-Sankyo Pharma Development, Munich, Germany (H.L.); and Daiichi-Sankyo Pharma Development, Edison, NJ (M.F.M.).
authors.forename: Ali
authors.initials: A
authors.lastname: Oto
authors.affiliation: From the Department of Medicine, UTSouthwestern Medical Center, Dallas, TX (M.S.L.); TIMI Study Group, Brigham and Women's Hospital, Boston, MA (R.P.G., C.T.R., B.M.S., A.E.C., S.A.M., E.M.A., E.B.); Department of Medicine, University of Oulu, Finland (H.H.); Oulu University Hospital, Finland (H.H.); Heart and Health Foundation of Turkey, Ankara (A.O.); Daiichi-Sankyo Pharma Development, Munich, Germany (H.L.); and Daiichi-Sankyo Pharma Development, Edison, NJ (M.F.M.).
authors.forename: Andrea E
authors.initials: AE
authors.lastname: Crompton
authors.affiliation: From the Department of Medicine, UTSouthwestern Medical Center, Dallas, TX (M.S.L.); TIMI Study Group, Brigham and Women's Hospital, Boston, MA (R.P.G., C.T.R., B.M.S., A.E.C., S.A.M., E.M.A., E.B.); Department of Medicine, University of Oulu, Finland (H.H.); Oulu University Hospital, Finland (H.H.); Heart and Health Foundation of Turkey, Ankara (A.O.); Daiichi-Sankyo Pharma Development, Munich, Germany (H.L.); and Daiichi-Sankyo Pharma Development, Edison, NJ (M.F.M.).
authors.forename: Sabina A
authors.initials: SA
authors.lastname: Murphy
authors.affiliation: From the Department of Medicine, UTSouthwestern Medical Center, Dallas, TX (M.S.L.); TIMI Study Group, Brigham and Women's Hospital, Boston, MA (R.P.G., C.T.R., B.M.S., A.E.C., S.A.M., E.M.A., E.B.); Department of Medicine, University of Oulu, Finland (H.H.); Oulu University Hospital, Finland (H.H.); Heart and Health Foundation of Turkey, Ankara (A.O.); Daiichi-Sankyo Pharma Development, Munich, Germany (H.L.); and Daiichi-Sankyo Pharma Development, Edison, NJ (M.F.M.).
authors.forename: Hans
authors.initials: H
authors.lastname: Lanz
authors.affiliation: From the Department of Medicine, UTSouthwestern Medical Center, Dallas, TX (M.S.L.); TIMI Study Group, Brigham and Women's Hospital, Boston, MA (R.P.G., C.T.R., B.M.S., A.E.C., S.A.M., E.M.A., E.B.); Department of Medicine, University of Oulu, Finland (H.H.); Oulu University Hospital, Finland (H.H.); Heart and Health Foundation of Turkey, Ankara (A.O.); Daiichi-Sankyo Pharma Development, Munich, Germany (H.L.); and Daiichi-Sankyo Pharma Development, Edison, NJ (M.F.M.).
authors.forename: Michele F
authors.initials: MF
authors.lastname: Mercuri
authors.affiliation: From the Department of Medicine, UTSouthwestern Medical Center, Dallas, TX (M.S.L.); TIMI Study Group, Brigham and Women's Hospital, Boston, MA (R.P.G., C.T.R., B.M.S., A.E.C., S.A.M., E.M.A., E.B.); Department of Medicine, University of Oulu, Finland (H.H.); Oulu University Hospital, Finland (H.H.); Heart and Health Foundation of Turkey, Ankara (A.O.); Daiichi-Sankyo Pharma Development, Munich, Germany (H.L.); and Daiichi-Sankyo Pharma Development, Edison, NJ (M.F.M.).
authors.forename: Elliott M
authors.initials: EM
authors.lastname: Antman
authors.affiliation: From the Department of Medicine, UTSouthwestern Medical Center, Dallas, TX (M.S.L.); TIMI Study Group, Brigham and Women's Hospital, Boston, MA (R.P.G., C.T.R., B.M.S., A.E.C., S.A.M., E.M.A., E.B.); Department of Medicine, University of Oulu, Finland (H.H.); Oulu University Hospital, Finland (H.H.); Heart and Health Foundation of Turkey, Ankara (A.O.); Daiichi-Sankyo Pharma Development, Munich, Germany (H.L.); and Daiichi-Sankyo Pharma Development, Edison, NJ (M.F.M.).
authors.forename: Eugene
authors.initials: E
authors.lastname: Braunwald
mesh_terms: D000368:Aged; D000925:Anticoagulants / Q000627:therapeutic use; D001281:Atrial Fibrillation / Q000150:complications* / Q000401:mortality* / Q000503:physiopathology; D065427:Factor Xa Inhibitors / Q000627:therapeutic use*; D005260:Female; D006470:Hemorrhage / Q000139:chemically induced; D006801:Humans; D008297:Male; D011725:Pyridines / Q000627:therapeutic use; D012307:Risk Factors; D020521:Stroke / Q000209:etiology* / Q000401:mortality* / Q000517:prevention & control; D013844:Thiazoles / Q000627:therapeutic use; D013923:Thromboembolism / Q000209:etiology* / Q000401:mortality* / Q000517:prevention & control; D016896:Treatment Outcome; D014859:Warfarin / Q000627:therapeutic use
chemical_list: D000925:Anticoagulants; D065427:Factor Xa Inhibitors; D011725:Pyridines; D013844:Thiazoles; D014859:Warfarin; C552171:edoxaban
keywords: atrial fibrillation; bleeding; mortality; stroke; thromboembolism