Author + information
- Received January 2, 2014
- Accepted January 30, 2014
- Published online August 1, 2014.
- Sammy Elmariah, MD, MPH∗,†,
- Anthony J. Furlan, MD‡,
- Mark Reisman, MD§,
- David Burke, MD†,
- Moshe Vardi, MD†,
- Neil J. Wimmer, MD‖,
- Shuqiong Ling, MS†,
- Xiaohua Chen, MA†,
- David M. Kent, MD, MSc¶,#,
- Joseph Massaro, PhD†∗∗,
- Laura Mauri, MD, MSc†,‖∗ (, )
- CLOSURE I Investigators
- ∗Cardiology Division, Department of Medicine, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts
- †Harvard Clinical Research Institute, Boston, Massachusetts
- ‡Neurology Department, University Hospital, Case Western Reserve University School of Medicine, Cleveland, Ohio
- §Division of Cardiology, University of Washington Medical Center, Seattle, Washington
- ‖Cardiology Division, Department of Medicine, Brigham and Women’s Hospital, Harvard Medical School, Boston, Massachusetts
- ¶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
- ∗∗Department of Biostatistics, Boston University School of Public Health, Boston, Massachusetts
- ↵∗Reprint requests and correspondence:
Dr. Laura Mauri, Brigham and Women’s Hospital, 75 Francis Street, Boston, Massachusetts 02115.
Objectives 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)
The CLOSURE I trial was supported by NMT Medical, Boston. Drs. Furlan and Reisman have received institutional research support from and have served as consultants for NMT Medical; and were principal investigators for the CLOSURE I trial. Dr. Kent has consulted for W. L. Gore Associates; and has received National Institutes of Healthhttp://dx.doi.org/10.13039/100000002/National Institute of Neurological Disorders and Strokehttp://dx.doi.org/10.13039/100000065 grants (#R21 NS079826, #R01 NS062153). Dr. Massaro has received institutional research support from NMT Medical; and has served as a consultant for Harvard Clinical Research Institute and NMT Medical. Dr. Mauri has received institutional research support from Abbott Vascular, Boston Scientific, Cordishttp://dx.doi.org/10.13039/100006479, Medtronichttp://dx.doi.org/10.13039/100004374, Bristol-Myers Squibbhttp://dx.doi.org/10.13039/100002491, Eli Lilly, Daiichi-Sankyohttp://dx.doi.org/10.13039/501100002973, and Sanofi-Aventis; and has served as a consultant to Biotronik, and St. Jude Medical. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose.
- Received January 2, 2014.
- Accepted January 30, 2014.
- American College of Cardiology Foundation