Percutaneous Closure of Patent Foramen Ovale in Cryptogenic Embolism

Closure, Anticoagulation, or Antiplatelet Therapy for Cryptogenic Stroke With Patent Foramen Ovale: Systematic Review of Randomized Trials, Sequential Meta‐Analysis, and New Insights From the CLOSE Study

“…We identified 9 articles reporting the results of 8 different RCTs meeting the inclusion criteria 7, 8, 9, 10, 11, 12, 30, 31. Four studies (CLOSURE I,7 PC trial,8 RESPECT,10 and DEFENSE‐PFO13) compared PFO closure with antithrombotic therapy (oral anticoagulation or antiplatelet therapy at the discretion of the investigator). Two studies (Gore REDUCE11 and CLOSE12) compared PFO closure with antiplatelet therapy.…”

“…The meta‐analysis of PFO closure versus antithrombotic therapy comprised a total of 3560 patients from 6 studies 7, 8, 10, 11, 12, 13. Key features of the design of included trials are summarized in Table.…”

“…The upper age limit for enrollment was 60 years in all trials except DEFENSE‐PFO, and median follow‐up duration ranged from 2 to 5.9 years (Table S2). Three trials (PC Trial,8 RESPECT,10 and DEFENSE‐PFO13) used the Amplatzer occluder device, the CLOSURE I study used the Starflex device,7 the Gore REDUCE study used the Cardioform or Helex device,11 and choice of the device was left to the discretion of the investigator in the CLOSE trial 12. For this analysis, the comparator was the one used in the design of each study: antiplatelet therapy or/and anticoagulation at the discretion of the investigator in CLOSURE I, PC Trial, RESPECT, and DEFENSE‐PFO; antiplatelet therapy in CLOSE and Gore REDUCE.…”

“…Observational studies have demonstrated a strong association between patent foramen ovale (PFO) and cryptogenic stroke,3, 4 suggesting that paradoxical embolism through a PFO may be an important cause of otherwise unexplained ischemic strokes, notably in younger patients 5, 6. Three randomized controlled trials (RCTs) published in 2012 and 2013 (CLOSURE I (STARFlex Septal Closure System in Patients with a Stroke and/or Transient Ischemic Attack due to Presumed Paradoxical Embolism through a Patent Foramen Ovale),7 PC Trial (Clinical Trial Comparing Percutaneous Closure of Patent Foramen Ovale Using the Amplatzer PFO Occluder with Medical Treatment in Patients with Cryptogenic Embolism),8 and RESPECT (Randomized Evaluation of Recurrent Stroke Comparing PFO Closure to Established Current Standard of Care Treatment)9) failed to demonstrate the superiority of PFO closure over antithrombotic therapy (antiplatelet therapy or anticoagulants) to prevent recurrent stroke. Recently, the long‐term analysis of the RESPECT trial10 and 3 other RCTs (Gore REDUCE (Gore Helex septal occluder and antiplatelet medical management for reduction of recurrent stroke or imaging‐confirmed transient ischemic attack in patients with patent foramen ovale),11 CLOSE (Patent Foramen Ovale Closure or Anticoagulants versus Antiplatelet Therapy to Prevent Stroke Recurrence),12 and DEFENSE‐PFO (Device Closure Versus Medical Therapy for Cryptogenic Stroke Patients With High Risk Patent Foramen Ovale)13) reported a lower incidence rate of recurrent stroke in patients randomized to PFO closure compared with controls.…”

Choice and Selection of Treatment Modalities for Cardiac Patients: An Interventional Cardiology Perspective

“…Taken together, the evidence from all 3 RCTs (Evaluation of the STARFlex Septal Closure System in Patients with a Stroke and/or Transient Ischemic Attack due to Presumed Paradoxical Embolism through a Patent Foramen Ovale‐CLOSURE I, Randomized evaluation of recurrent stroke comparing PFO closure to established current standard of care‐RESPECT, Percutaneous closure of PFO versus medical management in patients with cryptogenic stroke‐PC), each of which failed to demonstrate the benefit of transcatheter PFO closure over medical therapy, does not support the use of percutaneous closure for prevention of recurrent neurological events among patients with PFO and cryptogenic stroke 52, 53, 54. However, the per‐protocol analysis from RESPECT, which is at the root of ongoing controversy, leaves open the possibility that closure with an Amplatzer PFO occluder might be superior to medical therapy (primarily antiplatelet) in carefully screened patients with cryptogenic stroke 52.…”