Long-Term Outcomes of Patent Foramen Ovale Closure or Medical Therapy after Stroke

Abstract

Among adults who had had a cryptogenic ischemic stroke, closure of a PFO was associated with a lower rate of recurrent ischemic strokes than medical therapy alone during extended follow-up. (Funded by St. Jude Medical; RESPECT ClinicalTrials.gov number, NCT00465270 .).

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.…”

“…There was no blinding of participants and personnel to the treatment arm, but outcomes were adjudicated in a blinded fashion in all studies except in the DEFENSE‐PFO trial, for which this point was not specified in the original publication 13. The risk of attrition bias was judged sizeable in 3 of 6 studies, because of a relatively high dropout rate (>10%) in comparison to the low incidence of recurrent stroke, and a differential dropout rate between the closure and medical therapy arms 8, 10, 11. A possible selective reporting bias could not be excluded in the PC Trial because the Clinical Events Committee discounted potential primary end point events more often in the antithrombotic therapy group than in the PFO closure group 8, 32…”

“…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. We performed a systematic review and meta‐analysis of all randomized data allowing the direct comparison of PFO closure, anticoagulation, and antiplatelet therapy to prevent recurrent stroke in patients with cryptogenic stroke and PFO.…”