Direct oral anticoagulants versus vitamin K antagonists after recent ischemic stroke in patients with atrial fibrillation

Seiffge DJ, Paciaroni M, Wilson D, Koga M, Macha K, Cappellari M, Schaedelin S, Shakeshaft C, Takagi M, Tsivgoulis G, Bonetti B, Kallmünzer B, Arihiro S, Alberti A, Polymeris AA, Ambler G, Yoshimura S, Venti M, Bonati LH, Muir KW, Yamagami H, Thilemann S, Altavilla R, Peters N, Inoue M, Bobinger T, Agnelli G, Brown MM, Sato S, Acciarresi M, Jager HR, Bovi P, Schwab S, Lyrer P, Caso V, Toyoda K, Werring DJ, Engelter ST, De Marchis GM (2019)

Publication Type: Journal article

Publication year: 2019

Journal

Annals of Neurology Wiley-Blackwell

DOI: 10.1002/ana.25489

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.

Authors with CRIS profile

Kosmas Macha Medizinische Fakultät Bernd Kallmünzer Department of Neurology Stefan Schwab Lehrstuhl für Neurologie

Involved external institutions

Università degli Studi di Perugia IT Italy (IT) Universitäre Altersmedizin Felix Platter CH Switzerland (CH) Tecnológico de Monterrey (ITESM) MX Mexico (MX) Inselspital, Universitätsspital Bern CH Switzerland (CH) National and Kapodistrian University of Athens GR Greece (GR) University of Glasgow GB United Kingdom (GB) University Hospital of Verona / Azienda Ospedaliera Universitaria Integrata Verona (AOUI) IT Italy (IT) UCL Institute of Neurology GB United Kingdom (GB)

How to cite

APA:

Seiffge, D.J., Paciaroni, M., Wilson, D., Koga, M., Macha, K., Cappellari, M.,... De Marchis, G.M. (2019). Direct oral anticoagulants versus vitamin K antagonists after recent ischemic stroke in patients with atrial fibrillation. Annals of Neurology. https://dx.doi.org/10.1002/ana.25489

MLA:

Seiffge, David J., et al. "Direct oral anticoagulants versus vitamin K antagonists after recent ischemic stroke in patients with atrial fibrillation." Annals of Neurology (2019).

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