Anticoagulation in patients at high risk of stroke without documented atrial fibrillation. Time for a paradigm shift?

Atrial fibrillation (AF) is currently considered a risk factor for stroke. Depending on the severity of clinical factors (risk scores) a recommendation for full anticoagulation is made. Although AF is most certainly a risk factor for ischemic stroke, it is not necessarily the direct cause of it. The causality of association between AF and ischemic stroke is questioned by the reported lack of temporal relation between stroke events and AF paroxysms (or atrial high-rate episodes detected by devices). In different studies, only 2% of patients had subclinical AF > 6 minutes in duration at the time of stroke or systemic embolism. Is it time to consider AF only one more factor of endothelial disarray rather than the main contributor to stroke? In this "opinion paper" we propose to consider not only clinical variables predicting AF/stroke but also electrocardiographic markers of atrial fibrosis, as we postulate this as a strong indicator of risk of AF/stroke. We ask if it is time to change the paradigm and to consider, in some special situations, to protect patients (preventing stroke) who have no evidence of AF.