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Direct oral anticoagulants versus vitamin K antagonists after recent ischemic stroke in patients with atrial fibrillation
Author(s) -
Seiffge David J.,
Paciaroni Maurizio,
Wilson Duncan,
Koga Masatoshi,
Macha Kosmas,
Cappellari Manuel,
Schaedelin Sabine,
Shakeshaft Clare,
Takagi Masahito,
Tsivgoulis Georgios,
Bonetti Bruno,
Kallmünzer Bernd,
Arihiro Shoji,
Alberti Andrea,
Polymeris Alexandros A.,
Ambler Gareth,
Yoshimura Sohei,
Venti Michele,
Bonati Leo H.,
Muir Keith W.,
Yamagami Hiroshi,
Thilemann Sebastian,
Altavilla Riccardo,
Peters Nils,
Inoue Manabu,
Bobinger Tobias,
Agnelli Giancarlo,
Brown Martin M.,
Sato Shoichiro,
Acciarresi Monica,
Jager Hans Rolf,
Bovi Paolo,
Schwab Stefan,
Lyrer Philippe,
Caso Valeria,
Toyoda Kazunori,
Werring David J.,
Engelter Stefan T.,
De Marchis Gian Marco
Publication year - 2019
Publication title -
annals of neurology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 4.764
H-Index - 296
eISSN - 1531-8249
pISSN - 0364-5134
DOI - 10.1002/ana.25489
Subject(s) - medicine , interquartile range , atrial fibrillation , hazard ratio , intracerebral hemorrhage , vitamin k antagonist , stroke (engine) , proportional hazards model , warfarin , confidence interval , prospective cohort study , cardiology , subarachnoid hemorrhage , mechanical engineering , engineering
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.