title: Device closure of patent foramen ovale versus medical therapy in cryptogenic stroke: a systematic review and meta-analysis.
abstract: OBJECTIVE
  This study sought to perform a meta-analysis of randomized controlled trials comparing device closure with medical therapy in the prevention of recurrent neurological events in patients with cryptogenic stroke and patent foramen ovale.
  
  
  BACKGROUND
  The optimal strategy for secondary prevention of cryptogenic stroke with a patent foramen ovale is unclear.
  
  
  METHODS
  Several databases were searched from their inception to March 2013, which yielded 3 eligible studies. The results were pooled as per the different patient populations defined in the studies:-intention-to-treat, per-protocol, and as-treated cohorts. A generic inverse method was used based on time-to-event outcomes in a fixed-effect model. A supplementary analysis pooled the results from only 2 trials (RESPECT [Randomized Evaluation of Recurrent Stroke Comparing PFO Closure to Established Current Standard of Care Treatment] and PC Trial [Randomized Clinical Trial Comparing the Efficacy of Percutaneous Closure of Patent Foramen Ovale (PFO) With Medical Treatment in Patients With Cryptogenic Embolism]) as a similar device was used in them.
  
  
  RESULTS
  Our meta-analysis yielded effect-estimate hazard ratios of 0.67 (95% confidence interval [CI]: 0.44 to 1.00, I(2) = 0%) in the intention-to-treat cohort, 0.62 (95% CI: 0.40 to 0.95). I(2) = 0%) in the per-protocol cohort, and 0.61 (95% CI: 0.40 to 0.95, I(2) = 38%) in the as-treated cohort, showing beneficial effects of device closure. The results became more robust with pooled results from RESPECT and the PC Trial: The effect-estimate hazard ratios being 0.54 (95% CI: 0.29 to 1.01, I(2) = 0%), 0.48 (95% CI: 0.24 to 0.94, I(2) = 26%), and 0.42 (95% CI: 0.21 to 0.84, I(2) = 26%) in the intention-to-treat, per-protocol, and as-treated populations, respectively.
  
  
  CONCLUSIONS
  Our meta-analysis suggests that PFO closure is beneficial as compared to medical therapy in the prevention of recurrent neurological events. This meta-analysis helps to further strengthen the role of device closure in cryptogenic stroke.
authors.affiliation: Division of Cardiovascular Medicine, Department of Internal Medicine, University of Toledo Medical Center, Toledo, Ohio.
authors.forename: Abdur R
authors.initials: AR
authors.lastname: Khan
authors.affiliation: Department of Internal Medicine, University of Missouri-Kansas City, Kansas City, Missouri.
authors.forename: Aref A
authors.initials: AA
authors.lastname: Bin Abdulhak
authors.affiliation: Division of Cardiovascular Medicine, Department of Internal Medicine, University of Toledo Medical Center, Toledo, Ohio.
authors.forename: Mujeeb A
authors.initials: MA
authors.lastname: Sheikh
authors.affiliation: Division of Cardiovascular Medicine, Department of Internal Medicine, University of Toledo Medical Center, Toledo, Ohio.
authors.forename: Sobia
authors.initials: S
authors.lastname: Khan
authors.affiliation: Mayo Medical Library, Mayo Clinic, Rochester, Minnesota.
authors.forename: Patricia J
authors.initials: PJ
authors.lastname: Erwin
authors.affiliation: Department of Medicine, King Fahad Medical City, Riyadh, Kingdom of Saudi Arabia; Division of Infectious Diseases, Mayo Clinic, Rochester, Minnesota; Division of Epidemiology, Mayo Clinic, Rochester, Minnesota.
authors.forename: Imad
authors.initials: I
authors.lastname: Tleyjeh
authors.affiliation: Department of Medicine and Public Health, University of Toledo Medical Center, Toledo, Ohio.
authors.forename: Sadik
authors.initials: S
authors.lastname: Khuder
authors.affiliation: Division of Cardiovascular Medicine, Department of Internal Medicine, University of Toledo Medical Center, Toledo, Ohio. Electronic address: ehab.eltahawy2@utoledo.edu.
authors.forename: Ehab A
authors.initials: EA
authors.lastname: Eltahawy
mesh_terms: D000925:Anticoagulants / Q000627:therapeutic use*; D006328:Cardiac Catheterization / Q000295:instrumentation*; D016009:Chi-Square Distribution; D054092:Foramen Ovale, Patent / Q000150:complications / Q000175:diagnosis / Q000628:therapy*; D006801:Humans; D057194:Intention to Treat Analysis; D016017:Odds Ratio; D016016:Proportional Hazards Models; D016032:Randomized Controlled Trials as Topic; D012307:Risk Factors; D055502:Secondary Prevention / Q000295:instrumentation* / Q000379:methods; D055989:Septal Occluder Device; D020521:Stroke / Q000175:diagnosis / Q000209:etiology / Q000517:prevention & control*; D016896:Treatment Outcome
chemical_list: D000925:Anticoagulants
keywords: CI; HR; OR; PFO; TIA; confidence interval; cryptogenic stroke; device closure; hazard ratio; odds ratio; patent foramen ovale; recurrent stroke; transcatheter closure; transient ischemic attack