title: Predictors of recurrent events in patients with cryptogenic stroke and patent foramen ovale within the CLOSURE I (Evaluation of the STARFlex Septal Closure System in Patients With a Stroke and/or Transient Ischemic Attack Due to Presumed Paradoxical Embolism Through a Patent Foramen Ovale) trial.
abstract: OBJECTIVE
  This study sought to identify predictors of recurrent ischemic neurologic events within the CLOSURE I (Evaluation of the STARFlex Septal Closure System in Patients With a Stroke and/or Transient Ischemic Attack Due to Presumed Paradoxical Embolism Through a Patent Foramen Ovale) trial.
  
  
  BACKGROUND
  The CLOSURE I trial found that transcatheter patent foramen ovale (PFO) closure using the STARFlex device was not superior to medical therapy in patients with cryptogenic stroke or transient ischemic attack (TIA) and PFO.
  
  
  METHODS
  The CLOSURE I trial is a multicenter, randomized trial of transcatheter PFO closure compared with medical therapy in patients who presented with cryptogenic stroke or TIA and had a PFO. We identified clinical predictors of recurrent ischemic stroke or TIA during 2 years of follow-up using Cox proportional hazards regression within the pooled intention-to-treat cohort.
  
  
  RESULTS
  In 909 patients, the incidence of recurrent events was 5.7% with 25 patients suffering a recurrent stroke and 30 a TIA. Patients who had a recurrent event had higher body mass index (30.2 ± 6.2 vs. 28.3 ± 5.8%; p = 0.03) and more frequently had diabetes (19.2% vs. 7.1%; p = 0.0016), hypertension (46.2% vs. 30.1%; p = 0.015), and ischemic heart disease (3.8% vs. 0.9%; p = 0.05). Diabetes (hazard ratio [HR]: 3.39; 95% confidence interval [CI]: 1.69 to 6.84; p = 0.0007), index TIA (HR vs. stroke: 2.13; 95% CI: 1.20 to 3.80; p = 0.01), and the detection of atrial fibrillation after study enrollment (HR: 4.85; 95% CI: 2.05 to 11.47; p = 0.0003) independently predicted recurrent ischemic neurologic events. Recurrent neurologic events were more frequent in subjects with RoPE (Risk of Paradoxical Embolism) score ≤5 than those with >5 (14.5% vs. 4.2%; p < 0.0001).
  
  
  CONCLUSIONS
  These findings suggest an alternative etiology to paradoxical embolism was frequently responsible for recurrent events within the CLOSURE I trial. (Evaluation of the STARFlex Septal Closure System in Patients With a Stroke or TIA Due to the Possible Passage of a Clot of Unknown Origin Through a Patent Foramen Ovale (PFO) [CLOSURE I]; NCT00201461).
authors.affiliation: Cardiology Division, Department of Medicine, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts; Harvard Clinical Research Institute, Boston, Massachusetts.
authors.forename: Sammy
authors.initials: S
authors.lastname: Elmariah
authors.affiliation: Neurology Department, University Hospital, Case Western Reserve University School of Medicine, 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: Harvard Clinical Research Institute, Boston, Massachusetts.
authors.forename: David
authors.initials: D
authors.lastname: Burke
authors.affiliation: Harvard Clinical Research Institute, Boston, Massachusetts.
authors.forename: Moshe
authors.initials: M
authors.lastname: Vardi
authors.affiliation: Cardiology Division, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts.
authors.forename: Neil J
authors.initials: NJ
authors.lastname: Wimmer
authors.affiliation: Harvard Clinical Research Institute, Boston, Massachusetts.
authors.forename: Shuqiong
authors.initials: S
authors.lastname: Ling
authors.affiliation: Harvard Clinical Research Institute, Boston, Massachusetts.
authors.forename: Xiaohua
authors.initials: X
authors.lastname: Chen
authors.affiliation: Department of Neurology, Tufts Medical Center, Tufts University School of Medicine, Boston, Massachusetts; 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: David M
authors.initials: DM
authors.lastname: Kent
authors.affiliation: Harvard Clinical Research Institute, Boston, Massachusetts; Department of Biostatistics, Boston University School of Public Health, Boston, Massachusetts.
authors.forename: Joseph
authors.initials: J
authors.lastname: Massaro
authors.affiliation: Harvard Clinical Research Institute, Boston, Massachusetts; Cardiology Division, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts. Electronic address: lmauri1@partners.org.
authors.forename: Laura
authors.initials: L
authors.lastname: Mauri
mesh_terms: D000328:Adult; D006328:Cardiac Catheterization / Q000009:adverse effects / Q000295:instrumentation*; D016009:Chi-Square Distribution; D015897:Comorbidity; D019320:Embolism, Paradoxical / Q000175:diagnosis / Q000209:etiology / Q000517:prevention & control*; D005260:Female; D054092:Foramen Ovale, Patent / Q000150:complications / Q000175:diagnosis / Q000628:therapy*; D006801:Humans; D057194:Intention to Treat Analysis; D002546:Ischemic Attack, Transient / Q000175:diagnosis / Q000209:etiology / Q000517:prevention & control*; D008297:Male; D008875:Middle Aged; D015999:Multivariate Analysis; D016016:Proportional Hazards Models; D011446:Prospective Studies; D011474:Prosthesis Design; D012008:Recurrence; D012307:Risk Factors; D055502:Secondary Prevention / Q000295:instrumentation* / Q000379:methods; D055989:Septal Occluder Device; D020521:Stroke / Q000175:diagnosis / Q000209:etiology / Q000517:prevention & control*; D013997:Time Factors; D016896:Treatment Outcome; D014481:United States
keywords: patent foramen ovale; risk factor; stroke; transient ischemic attack