Subgroup analyses of the NAVIGATE ESUS study (Rivaroxaban Versus Aspirin in Secondary Prevention of Stroke and Prevention of Sys- temic Embolism in Patients With Recent Embolic Stroke of Undetermined Source) suggest that patients with left atrial diameter >4.6 cm may benefit from anticoagula- but those with PFO did not.784 A post hoc analysis of patients with ESUS enrolled in the SOCRATES trial (Soluble Guanylate Cyclase Stimulator in Heart Failure Studies) did not find an association between ticagrelor treatment and reduced vascular event risk.781 Ongoing randomized trials that may provide additional informa- tion about the efficacy of treatments to prevent recur- rent stroke among patients with ESUS include studies using prolonged rhythm monitoring to identify patients, studies that select patients with various markers of and trials that include MRI-defined CLINICAL STATEMENTS AND GUIDELINES Kleindorfer new ischemic events (silent strokes) as clinical trial Recommendation-Specific Supportive Text 1. The NAVIGATE ESUS and RESPECT ESUS (Dabigatran Etexilate for Secondary Stroke Prevention in Patients With Embolic Stroke of Undetermined Source) randomized trials found no reduction in secondary stroke risk among patients with ischemic stroke or TIA who were treated with a direct oral anticoagulant.779,780 2. A post hoc subgroup analysis of subjects with ESUS enrolled in the SOCRATES trial (4329 subjects, 32.8%) found no treatment effect by ESUS category of ticagrelor on recurrent vascu- lar event risk.781 Knowledge Gaps and Future Research Although ongoing trials may help address some of the questions about ESUS, knowledge gaps persist related to the definition of ESUS and optimal treatment for sec- ondary stroke prevention: What markers of atrial dysfunction are most strongly associated with recurrent stroke risk? Are there clinical factors that help identify patients with ESUS who may benefit from anticoagulation rather than antiplatelet treatment for secondary prevention? 