Revisiting the entity of embolic stroke of undetermined source

Abstract The term “embolic stroke of undetermined source” (ESUS) encompasses a sizable and heterogeneous population of patients with ischemic stroke. The introduction of the ESUS concept way back in 2014 opened up a new avenue to accommodate all ischemic stroke patients with an undetermined cause after the recommended diagnostic assessment. Several mechanisms can be the source of embolism in an ESUS patient, ranging from complex carotid plaque, aortic arch atheroma, patent foramen ovale, and left ventricular (LV) dysfunction to atrial cardiomyopathy, dysrhythmias, and cancer, found subsequently on rigorous evaluation. The clinical construct of ESUS aimed to define a subset of patients who might benefit from oral anticoagulation (OAC) rather than the standard antiplatelet therapy. However, all randomized controlled trials and meta-analyses have failed to demonstrate the superiority of OAC in ESUS, apart from a few post hoc analyses demonstrating the efficacy of OAC in specific subgroups like enlarged left atrium, LV dysfunction, and covert atrial fibrillation. Therefore, after assessing overall thromboembolic risk, it is wise to assemble a phenotypically similar patient population and randomize them to targeted preventive strategies rather than assuming that all will benefit from anticoagulation.