Figure S1. Flow diagram of study selection. Table S1. Main inclusion and exclusion criteria of included randomized trials. Table S2. Definitions of degree of shunting and atrial septal aneurysm in randomized trials. Table S3. Primary and secondary endpoints of included randomized trials. Table S4. Definitions of composite outcome, major bleeding, recurrent stroke and TIA in randomized trials. Table S5. Risk of bias of included randomized trials. Table S6. Study quality of included comparative observational studies using the Newcastle-Ottawa scale. Figure S2. The composite outcome of recurrent stroke, TIA and all-cause death with device closure versus medical therapy from randomized controlled trials and adjusted observational studies. Table S7. Subgroup analysis of the major outcomes based on study designs, number of patients and duration of follow-up. Table S8. Subgroup analysis of the composite outcome in randomized trials. Table S9. Subgroup analysis of recurrent ischemic stroke in randomized trials. Table...