COR LOE Recommendations Benefit B-R In patients with ESUS, treatment with direct oral anticoagulants is not recommended to reduce risk of secondary stroke.779,780 Benefit B-NR In patients with ESUS, treatment with ticagre- lor is not recommended to reduce the risk of Synopsis ESUS is an evolving stroke subtype commonly defined as a nonlacunar cryptogenic ischemic stroke. Lack of a standard definition has complicated studies of ESUS, with 1 review finding that many studies use variable diagnostic criteria, including type and duration of car- diac rhythm monitoring.782 This complexity in defining ESUS is one of the reasons proposed for the nega- tive clinical trials of anticoagulation compared with antiplatelet medication for stroke prevention779,780 and fuels much of the ongoing research to further define the association between markers of atrial cardiopathy and methods of assessing cardiac rhythm disorders and risk of recurrent stroke. 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. 