IJCS | Volume 33, Nº4, July and August 2020

310 Table 1 - The main aspects of selected studies Total number of patients Inclusion criteria Device and additional therapy Medical therapy Follow-up duration (years) Primary outcomes Level of significance adopted CLOSURE 1 (2012) 909 1. 18 to 60 y of age 2. PFO documented on TE 3. CS or TIA within the previous 6 mo STARFLex Septal Closure System + clopidogrel 75 mg/ day, 6 months, + aspirin, 81 or 325 mg/day, 2 years Aspirin or warfarin or both 2 A composite of stroke or TIA < 2 y and death (death for any cause < 30 d or death for neurologic causes between 31 d and 2 y) 5% RESPECT (2013) 980 1. 18 to 60 y of age 2. PFO documented on TE 3. CS within the previous 270 d Amplatzer PFO Occluder + 81 to 325 mg of aspirin plus clopidogrel for 1 month, followed by aspirin monotherapy for 5 months Aspirin or clopidogrel or aspirin + ER-dipyridamole or warfarin Mean: 2.6 ± 2.0 A composite of ischemic stroke or early death after randomization 5% PC TRIAL (2013) 414 1. < 60 y of age 2. PFO documented on TE 3. CS, TIA with cerebral ischemic lesion, or PTE Amplatzer PFO Occluder + 100-325 mg/day aspirin for at least 5 to 6 months + either 250-500 mg/d ticlopidine or 75-150 mg/day clopidogrel for 1 to 6 months Antiplatelet therapy or oral anticoagulation Mean: 4.1 a 4.0 b A composite of death, nonfatal stroke, TIA or peripheral embolism 5% CLOSE (2017) 663 1. 16 to 60 y of age 2. PFO with atrial septal aneurysm or large interatrial shunt 3. CS within the previous 6 mo One randomization arm: any of eleven different devices + dual antiplatelet therapy (75 mg of aspirin plus 75 mg of clopidogrel per day) for 3 months, followed by single antiplatelet therapy throughout the remainder of the trial Two further randomization arms: antiplatelet therapy alone (antiplatelet-only group), or oral anticoagulation (anticoagulation group). Antiplatelet regimen: aspirin, clopidogrel, or aspirin combined with ER- dipyridamole. Patients with contraindications to anticoagulants or to PFO closure were randomly assigned to the alternative noncontraindicated treatment or to antiplatelet therapy Mean: 5.3 ± 2.0 Fatal or nonfatal stroke. 5% Pereira et al. Patent foramen ovale in cryptogenic stroke Int J Cardiovasc Sci. 2020; 33(4):307-317 Original Article Medical Therapy for Cryptogenic Stroke Patients with High-Risk Patent Foramen Ovale”). The main aspects of the selected studies are shown in Table 1. In the closure group, device implantation was performed soon after randomization and, after the procedure, all patients were given antithrombotic therapy at the discretion of the site investigator, but always in accordance with the guideline recommendations. The mean follow-up duration varied between RCTs from 2 to 5.3 years. The data of patients enrolled in each RCT are listed in Table 2.After randomization, a total of 1,889 patients were assigned to closure arm and 1,671 patients were assigned