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

Seiffge, D. J. et al. (2019) Direct oral anticoagulants versus vitamin K antagonists after recent ischemic stroke in patients with atrial fibrillation. Annals of Neurology, 85(6), pp. 823-834. (doi: 10.1002/ana.25489) (PMID:30980560) (PMCID:PMC6563449)

Abstract

Objective: We compared outcomes after treatment with direct oral anticoagulants (DOAC) and Vitamin‐K antagonists (VKA) in patients with atrial fibrillation (AF) and a recent cerebral ischemia. Methods: We conducted an individual patient data analysis of 7 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 vs. 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 (HR) with 95% confidence intervals (95% CI). Results: We included 4912 patients (median age 78 years [IQR 71‐84]; 2331 [47.5%] women, median NIHSS at onset 5 [IQR 2‐12]); 2256 (45.9%) patients received VKA and 2656 (54.1%) DOAC. The median time from index event to starting oral anticoagulation was 5 days (IQR 2‐14) for VKA and 5 days (IQR 2‐11) for DOAC (p=0.53). There were 262 AIS (4.4%/year), 71 ICH (1.2%/year) and 439 deaths (7.4%/year) during the total follow‐up of 5970 patient‐years. Compared to VKA, 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 due to lower risks of ICH.

• Item Type: Articles
• Additional Information: D.J.S. is supported by a fellowship from the Swiss National Science Foundation (SNF), the Bangerter‐Rhyner Foundation, the Bayer Foundation 2017 “Thrombosis Research Award”, and the Swiss Society of Neurology. The NOACISP registry was supported by grants from the Swiss Heart Foundation, the Science Funds [Wissenschaftsfonds], the Bayer AG (Switzerland), and the Stroke Fund of the of the University Hospital Basel. The SAMURAI‐NVAF registry (M.K. and K.T.) is supported by a Grant‐in‐Aid (H23‐Junkanki‐Ippan‐010) from the Ministry of Health, Labour and Welfare, Japan and an Intramural Research Fund (H23‐4‐3 and H28‐4‐1) for Cardiovascular Diseases of the National Cerebral and Cardiovascular Center. CROMIS‐2 was jointly funded by the Stroke Association and the British Heart Foundation and supported by researchers at the National Institute for Health Research (NIHR) University College London Hospitals Biomedical Research Centre. UCL acted as the Sponsor for CROMIS‐2, with responsibility for the conduct and management of the study.
• Status: Published
• Refereed: Yes
• Glasgow Author(s) Enlighten ID: Muir, Professor Keith
• Authors: Seiffge, D. J., 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, A., Ambler, G., Yoshimura, S., Venti, M., Bonati, L., Muir, K. W., Yamagami, H., Thilemann, S., Altavilla, R., Peters, N., Inoue, M., Bobinger, S., Agnelli, G., Brown, M. M., Sato, S., Acciarresi, M., Jager, H. R., Bovi, P., Schwab, S., Lyrer, P., Caso, V., Toyoda, K., Werring, D., Engelter, S., and De Marchis, G. M.
• College/School: College of Medical Veterinary and Life Sciences > School of Psychology & Neuroscience
• Journal Name: Annals of Neurology
• Publisher: Wiley
• ISSN: 0364-5134
• ISSN (Online): 1531-8249
• Published Online: 13 April 2019
• Copyright Holders: Copyright © 2019 The Authors
• First Published: First published in Annals of Neurology 85(6):823-834
• Publisher Policy: Reproduced under a Creative Commons License