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A new clinical construct, embolic stroke of undetermined source (ESUS) was established as a therapeutically relevant entity, which are defined as a non-lacunar infarction without proximal arterial stenosis or cardioembolic sources, with a clear indication for anticoagulation, especially with direct oral anticoagulant (DOAC). The possible embolic sources include covert atrial fibrillation, arterial stenosis with <50%, low-risk emboligenic cardiac sources, aortic plaque, cancer-associated, and paradoxical embolism. As its diagnosis is based on exclusive process, ESUS comprises heterogeneous pathologies. Though current Japanese guideline recommends antiplatelets for non-cardioembolic stroke, ESUS may benefits from anticoagulants. Randomized trials testing DOAC for the secondary prevention of ESUS are currently ongoing.

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電子版ISSN 1344-8129 印刷版ISSN 1881-6096 医学書院