Embolic Stroke of Undetermined Source: JACC Review Topic of the Week

The term embolic stroke of undetermined source (ESUS) was introduced in 2014 to describe patients with a nonlacunar ischemic stroke and no convincing etiology. The terms ESUS and cryptogenic stroke are not synonyms, as the latter also includes patients with multiple stroke etiologies or incomplete diagnostic work-up. ESUS involves approximately 17% of all ischemic stroke patients, and these patients are typically younger with mild strokes and an annual rate of stroke recurrence of 4% to 5%. It was hypothesized that oral anticoagulation may decrease the risk of stroke recurrence in ESUS, which was tested in 2 large randomized controlled trials: the NAVIGATE ESUS (Rivaroxaban Versus Aspirin in Secondary Prevention of Stroke and Prevention of Systemic Embolism in Patients With Recent Embolic Stroke of Undetermined Source) and the RE-SPECT ESUS (Dabigatran Etexilate for Secondary Stroke Prevention in Patients With Embolic Stroke of Undetermined Source). The present review discusses the trials of anticoagulation in patients with ESUS, suggests potential explanations for their neutral results, and highlights the rationale that supports ongoing and future research in this population aiming to reduce the associated risk for stroke recurrence.