Beyond One-size-fits-all: Personalised ‘Tailored’ Approaches to Embolic Stroke of Undetermined Source

Background Embolic stroke of undetermined source (ESUS) is a significant subtype within the spectrum of cryptogenic strokes, defined by non-lacunar brain infarcts where there is no evidence of significant proximal large artery atherosclerosis or a major cardioembolic source like atrial fibrillation after a comprehensive diagnostic workup. Accounting for roughly 25% of ischaemic strokes, ESUS is associated with a substantial annual stroke recurrence rate of approximately 4.5%, contributing to 58% of stroke recurrence, which underscores the urgency for effective diagnostic and therapeutic interventions. However, the inherent variability of ESUS, where patients might harbour different underlying pathologies or risk factors, poses considerable challenges in both managing the acute phase and preventing further events. Recent clinical trials, such as NAVIGATE ESUS and ARCADIA, have explored the effectiveness of anticoagulation (AC) compared to antiplatelet (AP) therapy for secondary prevention, yet they have failed to establish a clear superior strategy, highlighting the limitations of a uniform treatment protocol. This review seeks to deepen the understanding of ESUS by critically appraising current diagnostic tools, management practices and preventive measures, advocating for a shift towards personalised treatment plans that take into account the unique clinical profile of each patient to optimise outcomes. Specialist Insight Trials over the last decade have not settled the ESUS treatment debate, yet they have underscored the importance of personalised medicine. The need for individualised AC or AP therapy for secondary prevention reflects this shift to precision medicine. Ongoing discussions about ESUS management highlight its heterogeneity, prompting research to establish clearer definitions of atrial cardiopathy and reduce overlap with other cardioembolic sources.