Stroke has traditionally been classified according to the trial of ORG 10172 in acute stroke treatment (TOAST) criteria; however, the concept of cryptogenic stroke did not meet the operational criteria necessary to define patient populations eligible for randomized studies. Therefore, the concept of embolic stroke of undetermined etiology (ESUS) was developed. An underlying hypothesis was that most strokes in patients with ESUS are caused by embolic events, hence, anticoagulation may prevent secondary events. Therefore, two large randomized trials were conducted comparing dabigatran or rivaroxaban with acetylsalicylic acid. Both studies could not show superiority of the new oral anticoagulants (NOAC) compared to aspirin; however, subgroup analyses showed that there is a patient population that may benefit from oral anticoagulation.
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