title: A novel risk prediction score in atrial fibrillation for a net clinical outcome from the ENGAGE AF-TIMI 48 randomized clinical trial.
abstract: OBJECTIVE
  The choice between initiating a non-vitamin K antagonist oral anticoagulant (NOAC) and a vitamin K antagonist (VKA) in patients with atrial fibrillation (AF) may be challenging. To assist in this decision, we developed a risk score to identify patients for whom a therapeutic benefit of NOACs over VKA is predicted.
  
  
  RESULTS
  ENGAGE AF-TIMI 48 was a randomized clinical trial of edoxaban vs. warfarin in 21 105 patients with AF. Cox proportional hazard models identified factors associated with a serious net clinical outcome (NCO) of disabling stroke, life-threatening bleeding, and all-cause mortality in VKA naïve patients from the warfarin arm. These were used to develop an integer risk score. Performance was assessed by C-indices and validation by bootstrapping. Kaplan-Meier analyses were stratified by three score categories and treatment arm. Over a median of 2.7 years, 457 NCO events occurred in 2898 patients with a total person-time of 7549.5 years (6.05%/year). The risk prediction model (C = 0.693) for the NCO was translated into a 17-point integer score, with annualized event rates for the low, intermediate, and high-risk categories in the warfarin arm of 3.5%, 9.9%, and 20.8%, respectively. Therapeutic benefit of higher- and lower-dose edoxaban over warfarin was demonstrated in the high- and intermediate-risk, with equal benefit in the low-risk categories (P-interaction 0.008 and 0.014, respectively).
  
  
  CONCLUSIONS
  In VKA naive patients with AF, the TIMI-AF score can assist in the prediction of a poor composite outcome and guide selection of anticoagulant therapy by identifying a differential clinical benefit with a NOAC or VKA.
authors.affiliation: Department of Medicine, TIMI Study Group, Cardiovascular Division, Brigham and Women's Hospital, Harvard Medical School, 350 Longwood Avenue, Boston, MA 02115, USA.
authors.forename: Christina L
authors.initials: CL
authors.lastname: Fanola
authors.affiliation: Department of Medicine, TIMI Study Group, Cardiovascular Division, Brigham and Women's Hospital, Harvard Medical School, 350 Longwood Avenue, Boston, MA 02115, USA.
authors.forename: Robert P
authors.initials: RP
authors.lastname: Giugliano
authors.affiliation: Department of Medicine, TIMI Study Group, Cardiovascular Division, Brigham and Women's Hospital, Harvard Medical School, 350 Longwood Avenue, Boston, MA 02115, USA.
authors.forename: Christian T
authors.initials: CT
authors.lastname: Ruff
authors.affiliation: Department of Medicine, TIMI Study Group, Cardiovascular Division, Brigham and Women's Hospital, Harvard Medical School, 350 Longwood Avenue, Boston, MA 02115, USA.
authors.forename: Marco
authors.initials: M
authors.lastname: Trevisan
authors.affiliation: Department of Medicine, TIMI Study Group, Cardiovascular Division, Brigham and Women's Hospital, Harvard Medical School, 350 Longwood Avenue, Boston, MA 02115, USA.
authors.forename: Francesco
authors.initials: F
authors.lastname: Nordio
authors.affiliation: Daiichi Sankyo Pharma Development 399 Thornall Street, Edison, NJ 08837, USA.
authors.forename: Michele F
authors.initials: MF
authors.lastname: Mercuri
authors.affiliation: Department of Medicine, TIMI Study Group, Cardiovascular Division, Brigham and Women's Hospital, Harvard Medical School, 350 Longwood Avenue, Boston, MA 02115, USA.
authors.forename: Elliott M
authors.initials: EM
authors.lastname: Antman
authors.affiliation: Department of Medicine, TIMI Study Group, Cardiovascular Division, Brigham and Women's Hospital, Harvard Medical School, 350 Longwood Avenue, Boston, MA 02115, USA.
authors.forename: Eugene
authors.initials: E
authors.lastname: Braunwald
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D000925:Anticoagulants / Q000627:therapeutic use*; D001281:Atrial Fibrillation / Q000150:complications*; D004311:Double-Blind Method; D065427:Factor Xa Inhibitors / Q000627:therapeutic use; D005260:Female; D006470:Hemorrhage / Q000139:chemically induced; D006801:Humans; D008297:Male; D008875:Middle Aged; D011725:Pyridines / Q000627:therapeutic use*; D018570:Risk Assessment; D012307:Risk Factors; D020521:Stroke / Q000517:prevention & control*; D013844:Thiazoles / Q000627:therapeutic use*; 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: Anticoagulants ; Atrial fibrillation ; Edoxaban; Stroke ; Warfarin 