title: Patent foramen ovale transcatheter closure vs. medical therapy on recurrent vascular events: a systematic review and meta-analysis of randomized controlled trials.
abstract: BACKGROUND
  In patients with cryptogenic stroke, transcatheter (TC) closure of a patent foramen ovale (PFO) has not been shown to better prevent recurrent vascular events than medical therapy. However, randomized controlled trials (RCT) to date have included few vascular events, and lack of power has been raised as an important concern.
  
  
  OBJECTIVE
  To conduct a systematic review and meta-analysis of existing RCT published studies assessing the recurrence of vascular events after TC PFO closure when compared to medical therapy.
  
  
  METHODS
  Using the search terms "patent foramen ovale", "PFO", "stroke", "percutaneous closure" and "transcatheter closure", Medline, Pubmed, Embase, and Cochrane databases were reviewed from inception through April 2013, with no language restrictions. Only studies in adult humans were considered. Additional references were obtained from the bibliographies of studies reviewed. The following criteria were used for study selection: 1) randomized controlled trial, 2) subjects were adult patients with cryptogenic stroke who were randomized to TC PFO closure or medical treatment (antiplatelet therapy and/or anticoagulation), and 3) reported outcomes included cardiac death, all death, stroke, transient ischemic attack, and peripheral embolism. Methodological and descriptive data, adverse events (including raw data and risk estimates), as well as procedural success and complications were abstracted in duplicate from each study independently, and agreement was tested. We followed rigorously the recommended guidelines for reporting and conducting and assessing quality of meta-analysis of RCT. The primary endpoints pre-specified in advance were recurrent vascular events, and composite endpoint of death, and recurrent vascular events.
  
  
  RESULTS
  Three studies were identified as meeting selection criteria. These included a total of 2,303 patients, with 1,150 patients randomized to TC PFO closure and 1,153 patients randomized to medical therapy. Mean follow-up was 3.5 years. Baseline characteristics (age, sex, and cardiovascular risk factors) were similar across studies. Intention-to-treat analyses showed a statistically significant risk reduction in stroke and/or transient ischemic attack in the TC PFO closure group when compared to medical treatment, pooled HR = 0.59, 95%CI (0.36-0.97), P = 0.04. The combined outcome of death, and vascular events, showed a borderline statistically significant benefit for TC PFO closure when compared to medical treatment, pooled HR = 0.67, 95%CI (0.44-1.00), P = 0.05 Subjects with a substantial PFO shunt seem to benefit the most with TC PFO closure, pooled HR = 0.35, 95%CI (0.12-1.03), P = 0.06, however, it did not reach statistical significance.
  
  
  CONCLUSIONS
  These results suggest that in patients with cryptogenic stroke, TC PFO closure may be beneficial in reducing the risk of recurrent vascular events when compared to medical treatment. The benefit of TC PFO closure may be greater in patients with a substantial shunt.
authors.affiliation: The Institute for Heart and Vascular Health and Cardiovascular Diseases, Einstein Medical Center, Philadelphia, PA, USA.
authors.forename: Pablo
authors.initials: P
authors.lastname: Rengifo-Moreno
authors.forename: Igor F
authors.initials: IF
authors.lastname: Palacios
authors.forename: Parichart
authors.initials: P
authors.lastname: Junpaparp
authors.forename: Christian F
authors.initials: CF
authors.lastname: Witzke
authors.forename: D Lynn
authors.initials: DL
authors.lastname: Morris
authors.forename: Abel
authors.initials: A
authors.lastname: Romero-Corral
mesh_terms: D000328:Adult; D000925:Anticoagulants / Q000627:therapeutic use*; D019917:Blood Vessel Prosthesis Implantation / Q000379:methods; D006328:Cardiac Catheterization / Q000009:adverse effects / Q000379:methods*; D005260:Female; D054092:Foramen Ovale, Patent / Q000628:therapy*; D006801:Humans; D008297:Male; D008875:Middle Aged; D010975:Platelet Aggregation Inhibitors / Q000627:therapeutic use*; D016032:Randomized Controlled Trials as Topic; D055502:Secondary Prevention; D055989:Septal Occluder Device; D020521:Stroke / Q000517:prevention & control; D016896:Treatment Outcome
chemical_list: D000925:Anticoagulants; D010975:Platelet Aggregation Inhibitors
keywords: PFO; Stroke; Transcatheter closure