Atrial Fibrillation and Ischemic Stroke despite Oral Anticoagulation

Patients with atrial fibrillation (AF) experiencing ischemic stroke despite oral anticoagulation (OAC), i.e., breakthrough strokes, are not uncommon, and represent an important clinical subgroup in view of the consistently high risk of stroke recurrence and mortality. The understanding of the heterogenous potential mechanism underlying OAC failure is essential in order to implement specific therapeutic measures aimed at reducing the risk of recurrent ischemic stroke. However, due to the incomplete comprehension of this phenomenon and the limited available data, secondary stroke prevention in such high-risk patients represents a clinical dilemma. There are several available strategies to prevent ischemic stroke recurrence in AF patients with breakthrough stroke in the absence of competing causes unrelated to AF, and these include continuation or change in the type of OAC, addition of antiplatelet therapy, left atrial appendage closure, or any combination of the above options. However, due to the limited available data, the latest guidelines do not provide any specific recommendations about which of the above strategies may be preferred. This review describes the incidence, the clinical impact and the potential mechanisms underlying OAC failure in AF patients. Furthermore, the evidence supporting each of the above therapeutic options for secondary stroke prevention and the potential future directions will be discussed.