Table 1.

Comparisons of PFO closure vs. drug treatment alone in patients with stroke and PFO.

Study	Patient's age	Qualifying cerebral event	Definition of high-risk PFO	Performed diagnostic workup	Device-related and drug treatment	Findings
DEFENSE-PFO (19) PFO closure vs. drug treatment (either antiplatelet therapy or anticoagulation)	≤ 60 years, mean age 51.8 years	Ischemic stroke (clinical symptoms ≥ 24 h or radiological evidence) within previous 6 months, classified as cryptogenic stroke	PFO and septal aneurysm ≥ 15 mm, septal hypermobility ≥ 10 mm or PFO size ≥ 2 mm at rest or during Valsalva maneuver	TEE protocol including the use of agitated saline, performed prior to randomization	PFO closure group: closure plus dual inhibition of platelet aggregation at least for 6 months (up to local investigator) Drug treatment group: Single or dual inhibition of platelet aggregation or Warfarin (chosen by the local investigator)	Rate of stroke recurrence was lower in the PFO closure group than the group receiving drug treatment alone
REDUCE (20) PFO closure (with two versions of a closure device) plus antiplatelet therapy vs. antiplatelet therapy alone	18–59 years, mean age 45.2 years	Ischemic stroke (clinical symptoms ≥ 24 h or radiological evidence) within previous 6 months, classified as cryptogenic stroke	PFO and right-to-left shunt, classified by the number of microbubbles in the left atrium	TEE protocol that focused on the existence of PFO and right-to-left shunt including the use of agitated saline, performed prior to randomization Assessment of septal aneurysm was done at the time of PFO closure and thus only in the closure group.	PFO closure group: closure plus inhibition of platelet aggregation with at least clopidogrel for 3 days and then resume or start another (not specified) inhibition of platelet aggregation Drug treatment group: Aspirin alone, aspirin and dipyridamole, or aspirin and clopidogrel (up to local investigator)	Risk of ischemic stroke was lower in the PFO closure group than the group receiving antiplatelet treatment alone
CLOSE (13) PFO closure or anticoagulation vs. antiplatelet therapy alone	16–60 years, no information regarding mean age	Ischemic stroke (clinical symptoms and radiological evidence) within previous 6 months, classified as cryptogenic stroke	PFO and septal aneurysm ≥ 10 mm or large right-to-left shunt, defined as more than 30 microbubbles in the left atrium	TEE protocol (contrast agent not specified), performed prior to study inclusion	PFO closure group: closure and dual inhibition of platelet aggregation for 3 months, followed by single antiplatelet therapy Anticoagulation group: vitamin K antagonists or direct oral anticoagulants Group with inhibition of platelet aggregation: Aspirin, clopidogrel or aspirin combined with dipyridamol	Lower rate of stroke in the group with PFO closure plus long-term antiplatelet therapy than with antiplatelet therapy alone The effects of oral anticoagulation as compared with antiplatelet therapy on the risk of stroke recurrence could not be determined