@article{2997803,
    title = "Direct oral anticoagulants versus vitamin K antagonists after recent ischemic stroke in patients with atrial fibrillation",
    author = "Seiffge, D.J. and Paciaroni, M. and Wilson, D. and Koga, M. and Macha, K. and Cappellari, M. and Schaedelin, S. and Shakeshaft, C. and Takagi, M. and Tsivgoulis, G. and Bonetti, B. and Kallmünzer, B. and Arihiro, S. and Alberti, A. and Polymeris, A.A. and Ambler, G. and Yoshimura, S. and Venti, M. and Bonati, L.H. and Muir, K.W. and Yamagami, H. and Thilemann, S. and Altavilla, R. and Peters, N. and Inoue, M. and Bobinger, T. and Agnelli, G. and Brown, M.M. and Sato, S. and Acciarresi, M. and Jager, H.R. and Bovi, P. and Schwab, S. and Lyrer, P. and Caso, V. and Toyoda, K. and Werring, D.J. and Engelter, S.T. and De Marchis, G.M. and on behalf of the CROMIS-2, RAF, RAF-DOAC, SAMURAI, NOACISP LONGTERM, Erlangen and Verona registry collaborators",
    journal = "Annals of Neurology",
    year = "2019",
    volume = "85",
    number = "6",
    pages = "823-834",
    publisher = "John Wiley and Sons Inc",
    issn = "0364-5134, 1531-8249",
    doi = "10.1002/ana.25489",
    keywords = "anticoagulant agent;  antivitamin K;  apixaban;  dabigatran;  edoxaban;  phenprocoumon;  rivaroxaban;  warfarin;  anticoagulant agent;  vitamin K group, aged;  anticoagulant therapy;  Article;  atrial fibrillation;  brain hemorrhage;  brain ischemia;  cohort analysis;  female;  follow up;  human;  major clinical study;  male;  mortality;  outcome assessment;  post hoc analysis;  priority journal;  prospective study;  risk reduction;  transient ischemic attack;  atrial fibrillation;  brain ischemia;  cerebrovascular accident;  comparative study;  oral drug administration;  very elderly, Administration, Oral;  Aged;  Aged, 80 and over;  Anticoagulants;  Atrial Fibrillation;  Brain Ischemia;  Cohort Studies;  Female;  Follow-Up Studies;  Humans;  Male;  Prospective Studies;  Stroke;  Vitamin K",
    abstract = "Objective: We compared outcomes after treatment with direct oral anticoagulants (DOACs) and vitamin K antagonists (VKAs) in patients with atrial fibrillation (AF) and a recent cerebral ischemia. Methods: We conducted an individual patient data analysis of seven prospective cohort studies. We included patients with AF and a recent cerebral ischemia (<3 months before starting oral anticoagulation) and a minimum follow-up of 3 months. We analyzed the association between type of anticoagulation (DOAC versus VKA) with the composite primary endpoint (recurrent ischemic stroke [AIS], intracerebral hemorrhage [ICH], or mortality) using mixed-effects Cox proportional hazards regression models; we calculated adjusted hazard ratios (HRs) with 95% confidence intervals (95% CIs). Results: We included 4,912 patients (median age, 78 years [interquartile range {IQR}, 71–84]; 2,331 [47.5%] women; median National Institute of Health Stroke Severity Scale at onset, 5 [IQR, 2–12]); 2,256 (45.9%) patients received VKAs and 2,656 (54.1%) DOACs. Median time from index event to starting oral anticoagulation was 5 days (IQR, 2–14) for VKAs and 5 days (IQR, 2–11) for DOACs (p = 0.53). There were 262 acute ischemic strokes (AISs; 4.4%/year), 71 intracranial hemorrrhages (ICHs; 1.2%/year), and 439 deaths (7.4%/year) during the total follow-up of 5,970 patient-years. Compared to VKAs, DOAC treatment was associated with reduced risks of the composite endpoint (HR, 0.82; 95% CI, 0.67–1.00; p = 0.05) and ICH (HR, 0.42; 95% CI, 0.24–0.71; p < 0.01); we found no differences for the risk of recurrent AIS (HR, 0.91; 95% CI, 0.70–1.19; p = 0.5) and mortality (HR, 0.83; 95% CI, 0.68–1.03; p = 0.09). Interpretation: DOAC treatment commenced early after recent cerebral ischemia related to AF was associated with reduced risk of poor clinical outcomes compared to VKA, mainly attributed to lower risks of ICH. ANN NEUROL 2019;85:823–834. © 2019 The Authors. Annals of Neurology published by Wiley Periodicals, Inc. on behalf of American Neurological Association."
}