Timing of oral anticoagulants initiation for atrial fibrillation after acute ischemic stroke: A systematic review and meta-analysis

Lina Palaiodimou; Maria-Ioanna Stefanou; Aristeidis H Katsanos; Gian Marco De Marchis; Diana Aguiar De Sousa; Jesse Dawson; Mira Katan; Theodore Karapanayiotides; Konstantinos Toutouzas; Maurizio Paciaroni; David J Seiffge; Georgios Tsivgoulis

doi:10.1177/23969873241251931

Timing of oral anticoagulants initiation for atrial fibrillation after acute ischemic stroke: A systematic review and meta-analysis

Eur Stroke J. 2024 May 14:23969873241251931. doi: 10.1177/23969873241251931. Online ahead of print.

Affiliations

¹ Second Department of Neurology, "Attikon" University Hospital, School of Medicine, National and Kapodistrian University of Athens, Athens, Greece.
² Department of Medicine (Neurology), McMaster University/Population Health Research Institute, Hamilton, Canada.
³ Department of Clinical Research, University of Basel, Basel, Switzerland.
⁴ Department of Neurology and Stroke Center, Kantonsspital St. Gallen, Switzerland.
⁵ Department of Neurosciences (Neurology), Hospital de Santa Maria, University of Lisbon, Lisbon, Portugal.
⁶ Institute of Cardiovascular and Medical Sciences, University of Glasgow, Glasgow, UK.
⁷ Department of Neurology, University Hospital of Zurich, Neuroscience Center Zurich, University of Zurich, Zurich, Switzerland.
⁸ Department of Neurology, University Hospital and University of Basel, Basel, Switzerland.
⁹ Second Department of Neurology, School of Medicine, Faculty of Health Sciences, AHEPA University General Hospital, Aristotle University of Thessaloniki, Thessaloniki, Greece.
¹⁰ First Department of Cardiology, National and Kapodistrian University of Athens, "Hippokration" Hospital, Athens, Greece.
¹¹ Stroke Unit and Division of Cardiovascular Medicine, University of Perugia, Italy.
¹² Department of Neurology, Inselspital, Bern University Hospital, University of Bern, Bern, Switzerland.

Abstract

Introduction: There is a longstanding clinical uncertainty regarding the optimal timing of initiating oral anticoagulants (OAC) for non-valvular atrial fibrillation following acute ischemic stroke. Current international recommendations are based on expert opinions, while significant diversity among clinicians is noted in everyday practice.

Methods: We conducted an updated systematic review and meta-analysis including all available randomized-controlled clinical trials (RCTs) and observational cohort studies that investigated early versus later OAC-initiation for atrial fibrillation after acute ischemic stroke. The primary outcome was defined as the composite of ischemic and hemorrhagic events and mortality at follow-up. Secondary outcomes included the components of the composite outcome (ischemic stroke recurrence, intracranial hemorrhage, major bleeding, and all-cause mortality). Pooled estimates were calculated with random-effects model.

Results: Nine studies (two RCTs and seven observational) were included comprising a total of 4946 patients with early OAC-initiation versus 4573 patients with later OAC-initiation following acute ischemic stroke. Early OAC-initiation was associated with reduced risk of the composite outcome (RR = 0.74; 95% CI:0.56-0.98; I² = 46%) and ischemic stroke recurrence (RR = 0.64; 95% CI:0.43-0.95; I² = 60%) compared to late OAC-initiation. Regarding safety outcomes, similar rates of intracranial hemorrhage (RR = 0.98; 95% CI:0.57-1.69; I² = 21%), major bleeding (RR = 0.78; 95% CI:0.40-1.51; I² = 0%), and mortality (RR = 0.94; 95% CI:0.61-1.45; I² = 0%) were observed. There were no subgroup differences, when RCTs and observational studies were separately evaluated.

Conclusions: Early OAC-initiation in acute ischemic stroke patients with non-valvular atrial fibrillation appears to have better efficacy and a similar safety profile compared to later OAC-initiation.

Keywords: Acute ischemic stroke; atrial fibrillation; intracerebral hemorrhage; meta-analysis; oral anticoagulants; secondary prevention.