Abstract
About 25% of ischaemic strokes are of cryptogenic origin and a significant proportion of them has a certain embolic nature, and for these patients the term embolic stroke of undetermined source (ESUS) has been coined. In the absence of subclinical atrial fibrillation (AF) identifiable through prolonged electrocardiogram monitoring, atrial cardiomyopathy, demonstrable through non-invasive cardiac imaging, aortic plaques and heart failure with preserved sinus rhythm, have been recognized among the potential causes of ESUS. In patients with ESUS, randomized clinical trials performed so far have failed to demonstrate a benefit of therapy with direct oral anticoagulants (DOACs). However, it is possible that in patients in whom the presence of atrial cardiomyopathy is ascertained there may be a benefit of anticoagulant therapy in secondary prevention after ESUS. In patients with aortic plaques associated with a thrombotic component and in those with heart failure and preserved sinus rhythm in the absence of AF but with a high congestive heart failure, hypertension age, diabetes, stroke, vascular disease (CHA2DS2-VASc) score, the decision on anticoagulant therapy with DOACs could be made in the individual patient even in the absence of evidence from clinical trials.