title: Device Closure of Patent Foramen Ovale After Stroke: Pooled Analysis of Completed Randomized Trials.
abstract: BACKGROUND
  The comparative effectiveness of percutaneous closure of patent foramen ovale (PFO) plus medical therapy versus medical therapy alone for cryptogenic stroke is uncertain.
  
  
  OBJECTIVE
  The authors performed the first pooled analysis of individual participant data from completed randomized trials comparing PFO closure versus medical therapy in patients with cryptogenic stroke.
  
  
  METHODS
  The analysis included data on 2 devices (STARFlex [umbrella occluder] [NMT Medical, Inc., Boston, Massachusetts] and Amplatzer PFO Occluder [disc occluder] [AGA Medical/St. Jude Medical, St. Paul, Minnesota]) evaluated in 3 trials. The primary composite outcome was stroke, transient ischemic attack, or death; the secondary outcome was stroke. We used log-rank tests and unadjusted and covariate-adjusted Cox regression models to compare device closure versus medical therapy.
  
  
  RESULTS
  Among 2,303 patients, closure was not significantly associated with the primary composite outcome. The difference became significant after covariate adjustment (hazard ratio [HR]: 0.68; p = 0.049). For the outcome of stroke, all comparisons were statistically significant, with unadjusted and adjusted HRs of 0.58 (p = 0.043) and 0.58 (p = 0.044), respectively. In analyses limited to the 2 disc occluder device trials, the effect of closure was not significant for the composite outcome, but was for the stroke outcome (unadjusted HR: 0.39; p = 0.013). Subgroup analyses did not identify significant heterogeneity of treatment effects. Atrial fibrillation was more common among closure patients.
  
  
  CONCLUSIONS
  Among patients with PFO and cryptogenic stroke, closure reduced recurrent stroke and had a statistically significant effect on the composite of stroke, transient ischemic attack, and death in adjusted but not unadjusted analyses.
authors.affiliation: Predictive Analytics and Comparative Effectiveness (PACE) Center, Institute for Clinical Research and Health Policy Studies, Tufts Medical Center/Tufts University School of Medicine, Boston, Massachusetts; Department of Neurology, Tufts Medical Center/Tufts University School of Medicine, Boston, Massachusetts. Electronic address: dkent1@tuftsmedicalcenter.org.
authors.forename: David M
authors.initials: DM
authors.lastname: Kent
authors.affiliation: Predictive Analytics and Comparative Effectiveness (PACE) Center, Institute for Clinical Research and Health Policy Studies, Tufts Medical Center/Tufts University School of Medicine, Boston, Massachusetts; Center for Evidence-based Medicine, School of Public Health, Brown University, Providence, Rhode Island; Department of Health Services, Policy & Practice, School of Public Health, Brown University, Providence, Rhode Island; Department of Epidemiology, School of Public Health, Brown University, Providence, Rhode Island.
authors.forename: Issa J
authors.initials: IJ
authors.lastname: Dahabreh
authors.affiliation: Predictive Analytics and Comparative Effectiveness (PACE) Center, Institute for Clinical Research and Health Policy Studies, Tufts Medical Center/Tufts University School of Medicine, Boston, Massachusetts.
authors.forename: Robin
authors.initials: R
authors.lastname: Ruthazer
authors.affiliation: Department of Neurology, Case Western Reserve University, Cleveland, Ohio.
authors.forename: Anthony J
authors.initials: AJ
authors.lastname: Furlan
authors.affiliation: Division of Cardiology, University of Washington Medical Center, Seattle, Washington.
authors.forename: Mark
authors.initials: M
authors.lastname: Reisman
authors.affiliation: Division of Cardiology, Department of Medicine, University of Colorado Denver, Aurora, Colorado.
authors.forename: John D
authors.initials: JD
authors.lastname: Carroll
authors.affiliation: Comprehensive Stroke Center and Department of Neurology, David Geffen School of Medicine/University of California Los Angeles, Los Angeles, California.
authors.forename: Jeffrey L
authors.initials: JL
authors.lastname: Saver
authors.affiliation: Division of Cardiology, Department of Medicine, The University of Texas Medical School at Houston, Houston, Texas.
authors.forename: Richard W
authors.initials: RW
authors.lastname: Smalling
authors.affiliation: Institute of Primary Health Care and Clinical Trials Unit Bern, University of Bern, Switzerland; Applied Health Research Centre (AHRC), Li Ka Shing Knowledge Institute of St. Michael's Hospital, University of Toronto, Ontario, Canada.
authors.forename: Peter
authors.initials: P
authors.lastname: Jüni
authors.affiliation: Department of Neurology, Bern University Hospital, Bern, Switzerland.
authors.forename: Heinrich P
authors.initials: HP
authors.lastname: Mattle
authors.affiliation: Department of Cardiology, Bern University Hospital, Bern, Switzerland.
authors.forename: Bernhard
authors.initials: B
authors.lastname: Meier
authors.affiliation: Department of Neurology, Tufts Medical Center/Tufts University School of Medicine, Boston, Massachusetts.
authors.forename: David E
authors.initials: DE
authors.lastname: Thaler
mesh_terms: D006328:Cardiac Catheterization / Q000379:methods*; D054092:Foramen Ovale, Patent / Q000150:complications / Q000601:surgery*; D006801:Humans; D015994:Incidence; D011475:Prosthesis Failure; D016032:Randomized Controlled Trials as Topic; D055989:Septal Occluder Device / Q000009:adverse effects*; D020521:Stroke / Q000453:epidemiology / Q000209:etiology / Q000628:therapy*; D015996:Survival Rate / Q000639:trends; D014481:United States / Q000453:epidemiology
keywords: cryptogenic stroke; meta-analysis; transient ischemic attack