David M Kent1,2, Jeffrey L Saver3, Robin Ruthazer1, Anthony J Furlan4, Mark Reisman5, John D Carroll6, Richard W Smalling7, Peter Jüni8, Heinrich P Mattle9, Bernhard Meier10, David E Thaler2. 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, MA. (D.M.K., R.R.). 2. Department of Neurology, Tufts Medical Center/Tufts University School of Medicine, Boston, MA. (D.M.K., D.E.T.). 3. Comprehensive Stroke Center and Department of Neurology, David Geffen School of Medicine/University of California Los Angeles (J.L.S.). 4. Department of Neurology, Case Western Reserve University, Cleveland, OH (A.J.F.). 5. Division of Cardiology, University of Washington Medical Center, Seattle (M.R.). 6. Division of Cardiology, Department of Medicine, University of Colorado Denver, Aurora (J.D.C.). 7. Division of Cardiology, Department of Medicine, University of Texas Medical School at Houston (R.W.S.). 8. Applied Health Research Centre (AHRC), Li Ka Shing Knowledge Institute of St. Michael's Hospital, Department of Medicine and Institute of Health Policy, Management and Evaluation, University of Toronto, ON, Canada (P.J.). 9. Department of Neurology, Bern University Hospital, Bern, Switzerland. (H.P.M.). 10. Department of Cardiology, Bern University Hospital, Bern, Switzerland. (B.M.).
Abstract
BACKGROUND AND PURPOSE: In patients with cryptogenic stroke and patent foramen ovale (PFO), the Risk of Paradoxical Embolism (RoPE) Score has been proposed as a method to estimate a patient-specific "PFO-attributable fraction"-the probability that a documented PFO is causally-related to the stroke, rather than an incidental finding. The objective of this research is to examine the relationship between this RoPE-estimated PFO-attributable fraction and the effect of closure in 3 randomized trials. METHODS: We pooled data from 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), RESPECT (Randomized Evaluation of Recurrent Stroke Comparing PFO Closure to Established Current Standard of Care Treatment), and PC (Clinical Trial Comparing Percutaneous Closure of Patent Foramen Ovale [PFO] Using the Amplatzer PFO Occluder With Medical Treatment in Patients With Cryptogenic Embolism) trials. We examine the treatment effect of closure in high RoPE score (≥7) versus low RoPE score (<7) patients. We also estimated the relative risk reduction associated with PFO closure across each level of the RoPE score using Cox proportional hazard analysis. We estimated a patient-specific attributable fraction using a PC trial-compatible (9-point) RoPE equation (omitting the neuroradiology variable), as well as a 2-trial analysis using the original (10-point) RoPE equation. We examined the Pearson correlation between the estimated attributable fraction and the relative risk reduction across RoPE strata. RESULTS: In the low RoPE score group (<7, n=912), the rate of recurrent strokes per 100 person-years was 1.37 in the device arm versus 1.68 in the medical arm (hazard ratio, 0.82 [0.42-1.59] P=0.56) compared with 0.30 versus 1.03 (hazard ratio, 0.31 [0.11-0.85] P=0.02) in the high RoPE score group (≥7, n=1221); treatment-by-RoPE score group interaction, P=0.12. The RoPE score estimated attributable fraction anticipated the relative risk reduction across all levels of the RoPE score, in both the 3-trial (r=0.95, P<0.001) and 2-trial (r=0.92, P<0.001) analyses. CONCLUSIONS: The RoPE score estimated attributable fraction is highly correlated to the relative risk reduction of device versus medical therapy. This observation suggests the RoPE score identifies patients with cryptogenic stroke who are likely to have a PFO that is pathogenic rather than incidental.
BACKGROUND AND PURPOSE: In patients with cryptogenic stroke and patent foramen ovale (PFO), the Risk of Paradoxical Embolism (RoPE) Score has been proposed as a method to estimate a patient-specific "PFO-attributable fraction"-the probability that a documented PFO is causally-related to the stroke, rather than an incidental finding. The objective of this research is to examine the relationship between this RoPE-estimated PFO-attributable fraction and the effect of closure in 3 randomized trials. METHODS: We pooled data from 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), RESPECT (Randomized Evaluation of Recurrent Stroke Comparing PFO Closure to Established Current Standard of Care Treatment), and PC (Clinical Trial Comparing Percutaneous Closure of Patent Foramen Ovale [PFO] Using the Amplatzer PFO Occluder With Medical Treatment in Patients With Cryptogenic Embolism) trials. We examine the treatment effect of closure in high RoPE score (≥7) versus low RoPE score (<7) patients. We also estimated the relative risk reduction associated with PFO closure across each level of the RoPE score using Cox proportional hazard analysis. We estimated a patient-specific attributable fraction using a PC trial-compatible (9-point) RoPE equation (omitting the neuroradiology variable), as well as a 2-trial analysis using the original (10-point) RoPE equation. We examined the Pearson correlation between the estimated attributable fraction and the relative risk reduction across RoPE strata. RESULTS: In the low RoPE score group (<7, n=912), the rate of recurrent strokes per 100 person-years was 1.37 in the device arm versus 1.68 in the medical arm (hazard ratio, 0.82 [0.42-1.59] P=0.56) compared with 0.30 versus 1.03 (hazard ratio, 0.31 [0.11-0.85] P=0.02) in the high RoPE score group (≥7, n=1221); treatment-by-RoPE score group interaction, P=0.12. The RoPE score estimated attributable fraction anticipated the relative risk reduction across all levels of the RoPE score, in both the 3-trial (r=0.95, P<0.001) and 2-trial (r=0.92, P<0.001) analyses. CONCLUSIONS: The RoPE score estimated attributable fraction is highly correlated to the relative risk reduction of device versus medical therapy. This observation suggests the RoPE score identifies patients with cryptogenic stroke who are likely to have a PFO that is pathogenic rather than incidental.
Authors: David M Kent; Issa J Dahabreh; Robin Ruthazer; Anthony J Furlan; Mark Reisman; John D Carroll; Jeffrey L Saver; Richard W Smalling; Peter Jüni; Heinrich P Mattle; Bernhard Meier; David E Thaler Journal: J Am Coll Cardiol Date: 2016-03-01 Impact factor: 24.094
Authors: Marie-Luise Mono; Laura Geister; Aekaterini Galimanis; Simon Jung; Fabien Praz; Marcel Arnold; Urs Fischer; Stefan Wolff; Oliver Findling; Stephan Windecker; Andreas Wahl; Bernhard Meier; Heinrich P Mattle; Krassen Nedeltchev Journal: Stroke Date: 2011-08-04 Impact factor: 7.914
Authors: Anthony J Furlan; Mark Reisman; Joseph Massaro; Laura Mauri; Harold Adams; Gregory W Albers; Robert Felberg; Howard Herrmann; Saibal Kar; Michael Landzberg; Albert Raizner; Lawrence Wechsler Journal: N Engl J Med Date: 2012-03-15 Impact factor: 91.245
Authors: Bernhard Meier; Bindu Kalesan; Heinrich P Mattle; Ahmed A Khattab; David Hildick-Smith; Dariusz Dudek; Grethe Andersen; Reda Ibrahim; Gerhard Schuler; Antony S Walton; Andreas Wahl; Stephan Windecker; Peter Jüni Journal: N Engl J Med Date: 2013-03-21 Impact factor: 91.245
Authors: David M Kent; Robin Ruthazer; Christian Weimar; Jean-Louis Mas; Joaquín Serena; Shunichi Homma; Emanuele Di Angelantonio; Marco R Di Tullio; Jennifer S Lutz; Mitchell S V Elkind; John Griffith; Cheryl Jaigobin; Heinrich P Mattle; Patrik Michel; Marie-Louise Mono; Krassen Nedeltchev; Federica Papetti; David E Thaler Journal: Neurology Date: 2013-07-17 Impact factor: 9.910
Authors: David M Kent; Jeffrey L Saver; Scott E Kasner; Jason Nelson; John D Carroll; Gilles Chatellier; Geneviève Derumeaux; Anthony J Furlan; Howard C Herrmann; Peter Jüni; Jong S Kim; Benjamin Koethe; Pil Hyung Lee; Benedicte Lefebvre; Heinrich P Mattle; Bernhard Meier; Mark Reisman; Richard W Smalling; Lars Soendergaard; Jae-Kwan Song; Jean-Louis Mas; David E Thaler Journal: JAMA Date: 2021-12-14 Impact factor: 157.335
Authors: Brian Mac Grory; Shadi Yaghi; Charlotte Cordonnier; Luciano A Sposato; Jose G Romano; Seemant Chaturvedi Journal: Circ Res Date: 2022-04-14 Impact factor: 23.213
Authors: Ernst Mayerhofer; Dirk Kanz; Brigitte Guschlbauer; Christopher D Anderson; Alexander Asmussen; Sebastian Grundmann; Christoph Strecker; Andreas Harloff Journal: Front Neurol Date: 2022-03-04 Impact factor: 4.003
Authors: Iain Willits; Kim Keltie; Robert Henderson; Mark de Belder; Nicholas Linker; Hannah Patrick; Helen Powell; Lee Berry; Samuel Urwin; Helen Cole; Andrew J Sims Journal: PLoS One Date: 2022-07-14 Impact factor: 3.752
Authors: Muhammad K Ahmed; Haris Kamal; Jessica L Weiss; Annemarie Crumlish; Peyman Shirani; Robert N Sawyer; Ashkan Mowla Journal: Brain Circ Date: 2021-05-29