PFO Closure, Oral Anticoagulants or Antiplatelet Therapy After PFO-associated Stroke in Patients Aged 60 to 80 Years

Time to disabling stroke

mRS score greater than or equal to 3, with an increase of at least 2 points compared to the last mRS score before the stroke.

Time frame: From date of randomization until the date of first recurrent disabling stroke, assessed from up to 4 years (for the last patient included) to up to 8 years (for the first patient included)

Time to ischemic stroke

At least one of the following criteria: * Sudden onset of focal neurological symptoms with the presence of cerebral infarction in the appropriate territory on brain imaging (CT or MRI), regardless of the duration of symptoms (less than or more than 24 hours). * Sudden onset of focal neurological symptoms lasting more than 24 hours, with no apparent cause other than cerebral ischemia.

Time frame: From date of randomization until the date of first recurrent ischemic stroke, assessed from up to 4 years (for the last patient included) to up to 8 years (for the first patient included)

Time to ischemic stroke or systemic embolism

Clinical features related to embolism usually affecting a limb, mesenteric, splenic, or renal artery. The diagnosis of embolism must be confirmed by appropriate investigations.

Time frame: From date of randomization until the date of first recurrent ischemic stroke or systemic embolism, assessed from up to 4 years (for the last patient included) to up to 8 years (for the first patient included)

Time to transient ischemic attack,

Sudden onset of neurological symptoms, presumed to be ischemic, resolving in less than 24 hours, clearly attributable to focal involvement of the central nervous system (or of the eye) with no signs of a corresponding recent cerebral infarction on brain imaging. The diagnosis of TIA will be confirmed by a neurologist, considering clinical data and brain imaging (MRI with diffusion sequence is recommended).

Time frame: From date of randomization until the date of first transient ischemic attack, assessed from up to 4 years (for the last patient included) to up to 8 years (for the first patient included)

Time to vascular death

* death related to a cardiac or vascular cause. * death due to hemorrhage. * death due to pulmonary embolism. * sudden death: death occurring in less than 24 hours, unexpectedly in a subject in apparent good health and whose condition was stable or was improving. * death with no documented non-vascular cause. * fatal stroke: death occurring within 30 days of a stroke (ischemic or hemorrhagic).

Time frame: From date of randomization until the date of vascular death, assessed from up to 4 years (for the last patient included) to up to 8 years (for the first patient included)

Time to all-cause mortality

Vascular (see definition) or nonvascular death: death due to a documented non-vascular cause (infection, cancer, accident, suicide, etc.).

Time frame: From date of randomization until the date of death, assessed from up to 4 years (for the last patient included) to up to 8 years (for the first patient included)

Quality of life score

Measured by using the European Quality Of Life (EQ-5D) auto-questionnaire. The digits for the five dimensions are combined into a 5-digit number that describes the patient's health state. The visual analogue scale (VAS) records the patient's self-rated health on a vertical axis from 0 (worst health) to 100 (best health)

Time frame: Every 6 months after randomization or up to 4 years (for the last patient included) to up to 8 years (for the first patient included)]

Time to fatal, life-threatening or major hemorrhage, including intracerebral and Intracranial hemorrhage

Life-threatening * Fatal hemorrhage. * Drop in hemoglobin by ≥ 5 g/dL (or drop in hematocrit by 15% or more in absolute value) * Symptomatic intracranial hemorrhage (confirmed by appropriate investigations, classified as cerebral hemorrhage, subarachnoid hemorrhage and subdural hematoma). * Transfusion ≥ 4 units of packed cells (or equivalent of whole blood)\*. Major * Transfusion ≤ 3 units of packed cells (or equivalent of whole blood)\*. * Requiring hospitalization (or prolonging hospitalization). * Requiring surgical treatment. * Intraocular hemorrhage with significant loss of vision. * Other hemorrhage responsible for significant disability according to the investigator.

Time frame: From date of randomization until the date of first fatal,life-threatening or major hemorrhage,including intracerebral and Intracranial hemorrhage,assessed from up to 4 years(for the last patient included) to up to 8 years(for the first patient included)

Proportion of success of device implantation, of the procedure and of PFO closure,

* Success of device implantation: deployment of the device in the appropriate place and removal of the placement system. * Success of the procedure: successful implantation with no complications before the patient's discharge. * Success of PFO closure: success of the procedure with no residual shunt or minimal residual shunt on echocardiography performed 6 months after the procedure.

Time frame: 6 months after PFO closure

Time to ischemic stroke recurrence according to the presence of a residual shunt

From control echocardiography after PFO closure to the end of the patient's follow-up

Time frame: From date of PFO closure until the date of first ischemic stroke recurrence, assessed from up to 4 years (for the last patient included) to up to 8 years (for the first patient included), according to the presence of residual shunt]

Time to new-onset atrial fibrillation

Atrial fibrillation lasting at least 30 seconds

Time frame: From date of randomization until the date of new-onset atrial fibrillation, assessed from up to 4 years (for the last patient included) to up to 8 years (for the first patient included)]

Proportion of fatal, life-threatening or major procedure- or device-related complications

Life-threatening * Cardiac perforation with tamponade requiring emergency drainage. * Cerebral air embolism responsible for acute neurological disorders * Embolization of the device. * Life-threatening hematoma at the puncture site or retroperitoneal. * Complications of general anesthesia or TOE requiring intensive care and/or surgical operation. Major * Hemorrhage at the puncture site or retroperitoneal requiring transfusion or surgery. * Arteriovenous fistula, pseudoaneurysm requiring surgery. * Peripheral nerve lesion with disabling neurological deficit persisting \> 1 month. * Cardiac arrhythmias (particularly AF) during catheterization or post-procedure requiring treatment \>= 1 month. * Infective endocarditis. * Asymptomatic late thrombosis of the device. * Any device-related complication requiring surgery. * Any other complication related to the transcatheter treatment or anesthesia, considered to be major by the investigator.

Time frame: Within 4 weeks following the procedure (PFO closure)

Costs

Costs will be estimated from the viewpoint of the healthcare system (hospital admission, transportation, study interventions, emergency room visit without admission,consultations,imaging)

Time frame: Within 48 months after randomization

Incremental cost-utility ratio at 4 years (ICUR)

The incremental cost-utility ratio (ICUR) will be calculated as difference in costs (between groups)/difference in QALYs (Quality-Adjusted Life Year) between groups. The QALYs will be constructed with the EuroQoL-5D (EQ-5D) questionnaire and value sets

Time frame: Within 48 months after randomization