Investigation and management of breakthrough ischemic stroke in anticoagulated patients with atrial fibrillation

Ischemic stroke is a serious complication of atrial fibrillation that is associated with substantial morbidity and mortality. For patients with non-valvular atrial fibrillation, treatment with a direct oral anticoagulant (DOAC) is first line treatment for stroke prevention. Ischemic strokes can still occur, however, despite appropriate anticoagulation-an event known as a breakthrough stroke. In this review, we provide an examination of breakthrough stroke through its epidemiology, mechanisms by which breakthrough strokes happen, and a framework for classification. We then propose a systematic, stepwise algorithm to investigate breakthrough stroke, including standardized criteria to identify an ideal population for future clinical trials using the AF-BREACH criteria (Atrial Fibrillation related BReakthrough Embolic Stroke despite appropriate anticoagulation without alternative Cause identified). Lastly, we discuss the emerging evidence for pharmacological and non-pharmacological management strategies.