Anticoagulation substantially reduces the risk of stroke in patients with atrial fibrillation (AF). However, recent studies have shown that up to 22%–36% of patients on anticoagulation will suffer an ischaemic stroke (IS). In this narrative review, we provide an overview of risk factors, mechanisms, management of acute IS and strategies for secondary prevention for patients with AF with stroke despite oral anticoagulation. For this paper, we reviewed available literature from important studies (randomised clinical trials, meta-analyses, reviews and case series) on patients with IS despite anticoagulation. We focused on recent studies that examined safety and efficacy of acute stroke treatments and evaluation and management strategies for secondary prevention. The literature review suggests that patients with AF with IS despite anticoagulation are a heterogeneous group with several possible mechanisms, which may include reduced or non-adherence to anticoagulation, competing non-cardioembolic stroke aetiologies or cardioembolic mechanisms separate from AF. The identification of one or more possible mechanisms of stroke despite anticoagulation may allow for a more targeted and individualised approach for secondary prevention. There are limited data to guide management in such patients, and strategies to prevent recurrent strokes include strict risk factor control and therapies targeting the most likely stroke mechanism. In cases where AF is suspected to be the culprit, clinical trials are needed to test the safety and efficacy of left atrial appendage occlusion plus anticoagulation versus continued anticoagulation alone.
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Contributors CS, TYW, DW, DJS, EES, MEG and SY contributed to manuscript preparation, revision, concept and design.
Funding The authors have not declared a specific grant for this research from any funding agency in the public, commercial or not-for-profit sectors.
Competing interests CS: received departmental funding from Massachusetts General Hospital for participation in the Neuro AFib study. SY: Medtronic (uncompensated). ESS: administers a research contract to the University of Calgary to provide brain MRI measurements to the Ottawa Heart Institute for the OCEAN clinical trial. MEG: received NIH grants and research funding to the hospital from AVID (a fully owned subsidiary of Eli Lilly), Boston Scientific (ISR) and Pfizer. DJS: advisory board fees (Portola/Alexion, Bayer Switzerland AG), unrestricted research grant (Portola/Alexion), academic research funds Swiss National Science Foundation, Bangerter Rhyner Foundation, Swiss Heart Foundation.
Provenance and peer review Commissioned; externally peer reviewed.