David M Kent1, Issa J Dahabreh2, Robin Ruthazer3, Anthony J Furlan4, Mark Reisman5, John D Carroll6, Jeffrey L Saver7, Richard W Smalling8, Peter Jüni9, Heinrich P Mattle10, Bernhard Meier11, David E Thaler12. 1. 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. 2. 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. 3. 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. 4. Department of Neurology, Case Western Reserve University, Cleveland, Ohio. 5. Division of Cardiology, University of Washington Medical Center, Seattle, Washington. 6. Division of Cardiology, Department of Medicine, University of Colorado Denver, Aurora, Colorado. 7. Comprehensive Stroke Center and Department of Neurology, David Geffen School of Medicine/University of California Los Angeles, Los Angeles, California. 8. Division of Cardiology, Department of Medicine, The University of Texas Medical School at Houston, Houston, Texas. 9. 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. 10. Department of Neurology, Bern University Hospital, Bern, Switzerland. 11. Department of Cardiology, Bern University Hospital, Bern, Switzerland. 12. Department of Neurology, Tufts Medical Center/Tufts University School of Medicine, Boston, Massachusetts.
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. OBJECTIVES: 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.
BACKGROUND: The comparative effectiveness of percutaneous closure of patent foramen ovale (PFO) plus medical therapy versus medical therapy alone for cryptogenic stroke is uncertain. OBJECTIVES: 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: Michelle H Leppert; Sharon N Poisson; John D Carroll; David E Thaler; Chong H Kim; Karen D Orjuela; P Michael Ho; James F Burke; Jonathan D Campbell Journal: Stroke Date: 2018-05-02 Impact factor: 7.914