title: Patent foramen ovale closure vs medical therapy for stroke prevention: meta-analysis of randomized trials and review of heterogeneity in meta-analyses.
abstract: BACKGROUND
  Patent foramen ovale (PFO) might be a risk factor for unexplained ("cryptogenic") stroke or transient ischemic attack (TIA). We sought to determine the efficacy and safety of transcatheter PFO closure compared with antithrombotic therapy for secondary prevention of cerebrovascular events among patients with cryptogenic stroke.
  
  
  METHODS
  We performed a systematic review and meta-analysis of MedLine and Embase (from inception to March 2013) for randomized controlled trials (RCTs) that compared transcatheter PFO closure with medical therapy in subjects with cryptogenic stroke. Data were independently extracted on trial conduct quality, baseline characteristics, efficacy, and safety events from published articles and appendices. Risk ratios (RRs) and 95% confidence intervals (CIs) for the composite of stroke or TIA, and adverse cardiovascular events including atrial fibrillation/flutter were constructed.
  
  
  RESULTS
  Three RCTs of 2303 subjects with previous stroke, TIA, or systemic arterial embolism (mean age, 45.7 years; 47.3% women; mean follow-up, 2.6 years) were included. PFO closure did not significantly reduce the risk of recurrent stroke/TIA (3.7% vs 5.2%; RR, 0.73; 95% CI, 0.50-1.07; P = 0.10); however, an increased risk of incident atrial fibrillation/flutter was detected (3.8% vs 1.0%; RR, 3.67; 95% CI, 1.95-6.89; P < 0.0001). No significant heterogeneity was detected for any end point among subgroups of patients stratified according to age, sex, index cardiovascular event, device type, interatrial shunt size, and presence of an atrial septal aneurysm (all P interactions ≥ 0.09).
  
  
  CONCLUSIONS
  Meta-analysis of RCTs that assessed transcatheter PFO closure for secondary prevention of cerebrovascular events in subjects with cryptogenic stroke does not demonstrate benefit compared with antithrombotic therapy, and suggests potential risks.
authors.affiliation: Cardiovascular Division, Department of Medicine, Women's College Hospital and University of Toronto, Toronto, Ontario, Canada. Electronic address: jay.udell@utoronto.ca.
authors.forename: Jacob A
authors.initials: JA
authors.lastname: Udell
authors.affiliation: Department of Cardiology, Boston Children's Hospital, and Harvard Medical School, Boston, Massachusetts, USA; Cardiovascular Division, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts, USA.
authors.forename: Alexander R
authors.initials: AR
authors.lastname: Opotowsky
authors.affiliation: Department of Cardiology, Boston Children's Hospital, and Harvard Medical School, Boston, Massachusetts, USA; Cardiovascular Division, Department of Medicine, Montreal Heart Institute and University of Montreal, Montreal, Québec, Canada.
authors.forename: Paul
authors.initials: P
authors.lastname: Khairy
authors.affiliation: Cardiovascular Division, Department of Medicine, Mount Sinai Hospital and Toronto General Hospital, University of Toronto, Toronto, Ontario, Canada.
authors.forename: Candice K
authors.initials: CK
authors.lastname: Silversides
authors.affiliation: Division of Neurology and Regional Stroke Centre, Department of Medicine, Sunnybrook Health Sciences Centre and University of Toronto, Toronto, Ontario, Canada.
authors.forename: David J
authors.initials: DJ
authors.lastname: Gladstone
authors.affiliation: Cardiovascular Division, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts, USA.
authors.forename: Patrick T
authors.initials: PT
authors.lastname: O'Gara
authors.affiliation: Department of Cardiology, Boston Children's Hospital, and Harvard Medical School, Boston, Massachusetts, USA; Cardiovascular Division, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts, USA.
authors.forename: Michael J
authors.initials: MJ
authors.lastname: Landzberg
mesh_terms: D005343:Fibrinolytic Agents / Q000627:therapeutic use*; D054092:Foramen Ovale, Patent / Q000150:complications* / Q000188:drug therapy / Q000628:therapy*; D006801:Humans; D002546:Ischemic Attack, Transient / Q000517:prevention & control; D019919:Prosthesis Implantation; D016032:Randomized Controlled Trials as Topic; D055989:Septal Occluder Device; D020521:Stroke / Q000517:prevention & control*; D015912:Thrombolytic Therapy; D016896:Treatment Outcome
chemical_list: D005343:Fibrinolytic Agents