The 15 min round table discussion by Christina Sjöstrand, Stockholm, Hans-Christoph Diener, Essen and George Ntaios, Thessaly, focuses on the concepts of randomized clinical trials for secondary stroke prevention in patients with embolic stroke of undetermined source (ESUS). Two large clinical trials tested the hypothesis that non-vitamin K antagonist oral anticoagulants (NOACs) might be superior to aspirin in preventing recurrent strokes after ESUS.

ESUS is a type of ischemic stroke with unknown origin, i.e. for which no probable cause can be identified after standard diagnostic evaluation. Thus, ESUS is a subgroup of cryptogenic stroke, which also includes strokes with incomplete evaluation and those for which more than one probable cause. Non-lacunar strokes in patients without no major-risk cardioembolic source (such as atrial fibrillation), no major atherosclerosis of the arteries supplying the brain infarct area and no other specific cause of their stroke are identified as ESUS.

Current strategy for secondary stroke prevention is based on antiplatelets but stroke recurrent rates remain high. A historical trial, WARSS, pointed at a potential advantage of anticoagulation over antiplatelet in patients with cryptogenic stroke. There is broad evidence for anticoagulation for stroke prevention in atrial fibrillation, thus providing another rationale for testing anticoagulation in ESUS.

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Two large trials randomized ESUS patients for long-term treatment with either a NOAC or aspirin: NAVIGATE ESUS was stopped after an interim analysis as efficacy was not different with rivaroxaban compared with aspirin but showed an increased risk of major bleeding. RE-SPECT ESUS is still ongoing as planned; in this trial dabigatran is tested against aspirin. Results will be presented in October 2018. If the trial is positive, i.e. showing greater efficacy of dabigatran in the prevention of stroke recurrence than aspirin, this may not only have great implications of how ESUS patients are treated but could also lead to a simplified post-stroke diagnostic workup for most patients with ischemic stroke.

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