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

The CLOSE trial (NCT00562289, NEJM 2017) has unambiguously demonstrated the superiority of patent foramen ovale (PFO) closure over antiplatelet therapy alone in patients aged up to 60 years with a PFO associated with an atrial septal aneurysm (ASA) or a large right-to-left shunt (so-called "high-risk PFO"), and an otherwise unexplained ischemic stroke. Oral anticoagulant therapy is also a logical approach assuming that PFO-related strokes are due to paradoxical embolism which implies a venous source of embolism, or to direct embolization of a thrombus formed at the atrial level. The CLOSE trial also suggested that oral anticoagulants might reduce stroke recurrence compared to aspirin.

There is accumulating evidence that presence of a PFO is significantly associated with cryptogenic stroke in patients over 60 years. Cryptogenic ischemic strokes represent about one third of all ischemic strokes in patients older than 60 years. However, the optimal therapeutic strategy in patients older than 60 years with a PFO and an otherwise unexplained ischemic stroke is unknown, because these patients were excluded from randomized trials.

The hypothesis tested in this trial is that transcatheter PFO closure plus long-term antiplatelet therapy is superior to antiplatelet therapy alone and that oral anticoagulant therapy is superior to antiplatelet therapy to prevent recurrent stroke in patients aged 60 to 80 years who have a high-risk PFO and a recent otherwise unexplained ischemic stroke.

• Time to disabling stroke [Срок оценки: 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 [Срок оценки: 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 [Срок оценки: 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, [Срок оценки: 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 [Срок оценки: 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 [Срок оценки: 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 [Срок оценки: 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 [Срок оценки: 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, [Срок оценки: 6 months after PFO closure]
• Time to ischemic stroke recurrence according to the presence of a residual shunt [Срок оценки: 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 [Срок оценки: 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 [Срок оценки: Within 4 weeks following the procedure (PFO closure)]