Medical Treatment With or Without Transcatheter Patent Foramen Ovale Closure (STOP)

Inclusion Criteria: Cryptogenic stroke Age >60 years Right-to-left shunt as evaluated by echocardiography (TEE). Exclusion Criteria: -≤60 year-old Lacunar (small vessel) stroke. Permanent or paroxysmal atrial fibrillation/flutter (clinically apparent or detected by continuous ECG monitoring). Need for chronic anticoagulation therapy. Any contraindication for antiplatelet therapy (aspirin, clopidogrel, ticagrelor). Presence of extracranial or intracranial atherosclerosis causing ≥50% luminal --stenosis in arteries supplying the area of ischemia. Presence of complex atheroma plaques at the ascending aorta-aortic arch (≥4-mm-thick, ulcerated or containing mobile thrombi) as evaluated by TEE. Presence of intracardiac thrombus as evaluated by TEE. Uncontrolled hypertension (systemic pressure values >160/90 mmHg despite optimal medical treatment). History of myocardial infarction or coronary intervention. (percutaneous coronary intervention, coronary artery bypass graft). History of prior valve surgery or transcatheter valve repair. Presence of deep venous thrombosis at the time of index stroke as evaluated by Doppler ultrasonography. Left ventricular ejection fraction <50% as evaluated by TTE. Significant (moderate or severe) valvular disease as evaluated by echocardiography. History of congestive heart failure. Severe chronic kidney dysfunction defined an estimated glomerular filtration rate <30 ml/min/m2 or need for dialysis. Isolated ASD or ASD associated with PFO but with a hemodynamically significant left-to-right shunt requiring closure. Other specific cause of stroke identified (eg, arteritis, dissection, migraine/vasospasm, and drug abuse). Prior surgical or endovascular treatments of PFO or ASD. Rheumatic heart disease. Left atrial enlargement defined as a left atrial diameter >41 mm in men and ≥39 mm in women. Presence of high burden of premature atrial contractions (>500 per 24 hrs) as evaluated by continuous ECG monitoring. Follow-up impossible or expected poor compliance. Active cancer. Presence of an inferior vena cava filter. Severe pulmonary artery hypertension (systolic pulmonary pressure >60 mmHg). Functional dependency as measured by a modified Rankin Scale score >3 (unable to attend to own bodily needs without assistance and unable to walk unassisted). Any medical condition determining a life expectancy <2 years. Participation in another randomized study. Failure to provide signed informed consent.