title: Determinants of antithrombotic choice for patent foramen ovale in cryptogenic stroke.
abstract: OBJECTIVE
  We examined the influence of clinical, radiologic, and echocardiographic characteristics on antithrombotic choice in patients with cryptogenic stroke (CS) and patent foramen ovale (PFO), hypothesizing that features suggestive of paradoxical embolism might lead to greater use of anticoagulation.
  
  
  METHODS
  The Risk of Paradoxical Embolism Study combined 12 databases to create the largest dataset of patients with CS and known PFO status. We used generalized linear mixed models with a random effect of component study to explore whether anticoagulation was preferentially selected based on the following: (1) younger age and absence of vascular risk factors, (2) "high-risk" echocardiographic features, and (3) neuroradiologic findings.
  
  
  RESULTS
  A total of 1,132 patients with CS and PFO treated with anticoagulation or antiplatelets were included. Overall, 438 participants (39%) were treated with anticoagulation with a range (by database) of 22% to 54%. Treatment choice was not influenced by age or vascular risk factors. However, neuroradiologic findings (superficial or multiple infarcts) and high-risk echocardiographic features (large shunts, shunt at rest, and septal hypermobility) were predictors of anticoagulation use.
  
  
  CONCLUSIONS
  Both antithrombotic regimens are widely used for secondary stroke prevention in patients with CS and PFO. Radiologic and echocardiographic features were strongly associated with treatment choice, whereas conventional vascular risk factors were not. Prior observational studies are likely to be biased by confounding by indication.
authors.affiliation: From the Department of Neurology (D.E.T., D.M.K.), and Predictive Analytics and Comparative Effectiveness Center, Institute for Clinical Research and Health Policy Studies (R.R., J.S.L., D.M.K.), Tufts Medical Center/Tufts University School of Medicine, Boston, MA; Department of Neurology, University of Duisburg-Essen (C.W.), Germany; Neurology Department at the Hospital Universitari Doctor Josep Trueta Institut d'Investigació Biomèdica de Girona (J.S.), Spain; Department of Neurology, Inselspital (H.P.M., M.-L.M.), University of Bern; Division of Neurology at the Triemli Municipal Hospital (K.N.), Zurich, Switzerland; Department of Public Health and Primary Care (E.D.A.), Cambridge University, UK; Departments of Neurology and Epidemiology (M.S.V.E.), and Division of Cardiology (M.R.D.T., S.H.), Columbia University, NY; Neurology Service, Centre Hospitalier Universitaire Vaudois (P.M.), Switzerland; Department of Cardiology (B.M.), Swiss Cardiovascular Center, Inselspital, University of Bern, Switzerland; and Department of Neurology (A.J.F.), Case Western Reserve University, Cleveland, OH. dthaler@tuftsmedicalcenter.org.
authors.forename: David E
authors.initials: DE
authors.lastname: Thaler
authors.affiliation: From the Department of Neurology (D.E.T., D.M.K.), and Predictive Analytics and Comparative Effectiveness Center, Institute for Clinical Research and Health Policy Studies (R.R., J.S.L., D.M.K.), Tufts Medical Center/Tufts University School of Medicine, Boston, MA; Department of Neurology, University of Duisburg-Essen (C.W.), Germany; Neurology Department at the Hospital Universitari Doctor Josep Trueta Institut d'Investigació Biomèdica de Girona (J.S.), Spain; Department of Neurology, Inselspital (H.P.M., M.-L.M.), University of Bern; Division of Neurology at the Triemli Municipal Hospital (K.N.), Zurich, Switzerland; Department of Public Health and Primary Care (E.D.A.), Cambridge University, UK; Departments of Neurology and Epidemiology (M.S.V.E.), and Division of Cardiology (M.R.D.T., S.H.), Columbia University, NY; Neurology Service, Centre Hospitalier Universitaire Vaudois (P.M.), Switzerland; Department of Cardiology (B.M.), Swiss Cardiovascular Center, Inselspital, University of Bern, Switzerland; and Department of Neurology (A.J.F.), Case Western Reserve University, Cleveland, OH.
authors.forename: Robin
authors.initials: R
authors.lastname: Ruthazer
authors.affiliation: From the Department of Neurology (D.E.T., D.M.K.), and Predictive Analytics and Comparative Effectiveness Center, Institute for Clinical Research and Health Policy Studies (R.R., J.S.L., D.M.K.), Tufts Medical Center/Tufts University School of Medicine, Boston, MA; Department of Neurology, University of Duisburg-Essen (C.W.), Germany; Neurology Department at the Hospital Universitari Doctor Josep Trueta Institut d'Investigació Biomèdica de Girona (J.S.), Spain; Department of Neurology, Inselspital (H.P.M., M.-L.M.), University of Bern; Division of Neurology at the Triemli Municipal Hospital (K.N.), Zurich, Switzerland; Department of Public Health and Primary Care (E.D.A.), Cambridge University, UK; Departments of Neurology and Epidemiology (M.S.V.E.), and Division of Cardiology (M.R.D.T., S.H.), Columbia University, NY; Neurology Service, Centre Hospitalier Universitaire Vaudois (P.M.), Switzerland; Department of Cardiology (B.M.), Swiss Cardiovascular Center, Inselspital, University of Bern, Switzerland; and Department of Neurology (A.J.F.), Case Western Reserve University, Cleveland, OH.
authors.forename: Christian
authors.initials: C
authors.lastname: Weimar
authors.affiliation: From the Department of Neurology (D.E.T., D.M.K.), and Predictive Analytics and Comparative Effectiveness Center, Institute for Clinical Research and Health Policy Studies (R.R., J.S.L., D.M.K.), Tufts Medical Center/Tufts University School of Medicine, Boston, MA; Department of Neurology, University of Duisburg-Essen (C.W.), Germany; Neurology Department at the Hospital Universitari Doctor Josep Trueta Institut d'Investigació Biomèdica de Girona (J.S.), Spain; Department of Neurology, Inselspital (H.P.M., M.-L.M.), University of Bern; Division of Neurology at the Triemli Municipal Hospital (K.N.), Zurich, Switzerland; Department of Public Health and Primary Care (E.D.A.), Cambridge University, UK; Departments of Neurology and Epidemiology (M.S.V.E.), and Division of Cardiology (M.R.D.T., S.H.), Columbia University, NY; Neurology Service, Centre Hospitalier Universitaire Vaudois (P.M.), Switzerland; Department of Cardiology (B.M.), Swiss Cardiovascular Center, Inselspital, University of Bern, Switzerland; and Department of Neurology (A.J.F.), Case Western Reserve University, Cleveland, OH.
authors.forename: Joaquín
authors.initials: J
authors.lastname: Serena
authors.affiliation: From the Department of Neurology (D.E.T., D.M.K.), and Predictive Analytics and Comparative Effectiveness Center, Institute for Clinical Research and Health Policy Studies (R.R., J.S.L., D.M.K.), Tufts Medical Center/Tufts University School of Medicine, Boston, MA; Department of Neurology, University of Duisburg-Essen (C.W.), Germany; Neurology Department at the Hospital Universitari Doctor Josep Trueta Institut d'Investigació Biomèdica de Girona (J.S.), Spain; Department of Neurology, Inselspital (H.P.M., M.-L.M.), University of Bern; Division of Neurology at the Triemli Municipal Hospital (K.N.), Zurich, Switzerland; Department of Public Health and Primary Care (E.D.A.), Cambridge University, UK; Departments of Neurology and Epidemiology (M.S.V.E.), and Division of Cardiology (M.R.D.T., S.H.), Columbia University, NY; Neurology Service, Centre Hospitalier Universitaire Vaudois (P.M.), Switzerland; Department of Cardiology (B.M.), Swiss Cardiovascular Center, Inselspital, University of Bern, Switzerland; and Department of Neurology (A.J.F.), Case Western Reserve University, Cleveland, OH.
authors.forename: Heinrich P
authors.initials: HP
authors.lastname: Mattle
authors.affiliation: From the Department of Neurology (D.E.T., D.M.K.), and Predictive Analytics and Comparative Effectiveness Center, Institute for Clinical Research and Health Policy Studies (R.R., J.S.L., D.M.K.), Tufts Medical Center/Tufts University School of Medicine, Boston, MA; Department of Neurology, University of Duisburg-Essen (C.W.), Germany; Neurology Department at the Hospital Universitari Doctor Josep Trueta Institut d'Investigació Biomèdica de Girona (J.S.), Spain; Department of Neurology, Inselspital (H.P.M., M.-L.M.), University of Bern; Division of Neurology at the Triemli Municipal Hospital (K.N.), Zurich, Switzerland; Department of Public Health and Primary Care (E.D.A.), Cambridge University, UK; Departments of Neurology and Epidemiology (M.S.V.E.), and Division of Cardiology (M.R.D.T., S.H.), Columbia University, NY; Neurology Service, Centre Hospitalier Universitaire Vaudois (P.M.), Switzerland; Department of Cardiology (B.M.), Swiss Cardiovascular Center, Inselspital, University of Bern, Switzerland; and Department of Neurology (A.J.F.), Case Western Reserve University, Cleveland, OH.
authors.forename: Krassen
authors.initials: K
authors.lastname: Nedeltchev
authors.affiliation: From the Department of Neurology (D.E.T., D.M.K.), and Predictive Analytics and Comparative Effectiveness Center, Institute for Clinical Research and Health Policy Studies (R.R., J.S.L., D.M.K.), Tufts Medical Center/Tufts University School of Medicine, Boston, MA; Department of Neurology, University of Duisburg-Essen (C.W.), Germany; Neurology Department at the Hospital Universitari Doctor Josep Trueta Institut d'Investigació Biomèdica de Girona (J.S.), Spain; Department of Neurology, Inselspital (H.P.M., M.-L.M.), University of Bern; Division of Neurology at the Triemli Municipal Hospital (K.N.), Zurich, Switzerland; Department of Public Health and Primary Care (E.D.A.), Cambridge University, UK; Departments of Neurology and Epidemiology (M.S.V.E.), and Division of Cardiology (M.R.D.T., S.H.), Columbia University, NY; Neurology Service, Centre Hospitalier Universitaire Vaudois (P.M.), Switzerland; Department of Cardiology (B.M.), Swiss Cardiovascular Center, Inselspital, University of Bern, Switzerland; and Department of Neurology (A.J.F.), Case Western Reserve University, Cleveland, OH.
authors.forename: Marie-Luise
authors.initials: ML
authors.lastname: Mono
authors.affiliation: From the Department of Neurology (D.E.T., D.M.K.), and Predictive Analytics and Comparative Effectiveness Center, Institute for Clinical Research and Health Policy Studies (R.R., J.S.L., D.M.K.), Tufts Medical Center/Tufts University School of Medicine, Boston, MA; Department of Neurology, University of Duisburg-Essen (C.W.), Germany; Neurology Department at the Hospital Universitari Doctor Josep Trueta Institut d'Investigació Biomèdica de Girona (J.S.), Spain; Department of Neurology, Inselspital (H.P.M., M.-L.M.), University of Bern; Division of Neurology at the Triemli Municipal Hospital (K.N.), Zurich, Switzerland; Department of Public Health and Primary Care (E.D.A.), Cambridge University, UK; Departments of Neurology and Epidemiology (M.S.V.E.), and Division of Cardiology (M.R.D.T., S.H.), Columbia University, NY; Neurology Service, Centre Hospitalier Universitaire Vaudois (P.M.), Switzerland; Department of Cardiology (B.M.), Swiss Cardiovascular Center, Inselspital, University of Bern, Switzerland; and Department of Neurology (A.J.F.), Case Western Reserve University, Cleveland, OH.
authors.forename: Emanuele
authors.initials: E
authors.lastname: Di Angelantonio
authors.affiliation: From the Department of Neurology (D.E.T., D.M.K.), and Predictive Analytics and Comparative Effectiveness Center, Institute for Clinical Research and Health Policy Studies (R.R., J.S.L., D.M.K.), Tufts Medical Center/Tufts University School of Medicine, Boston, MA; Department of Neurology, University of Duisburg-Essen (C.W.), Germany; Neurology Department at the Hospital Universitari Doctor Josep Trueta Institut d'Investigació Biomèdica de Girona (J.S.), Spain; Department of Neurology, Inselspital (H.P.M., M.-L.M.), University of Bern; Division of Neurology at the Triemli Municipal Hospital (K.N.), Zurich, Switzerland; Department of Public Health and Primary Care (E.D.A.), Cambridge University, UK; Departments of Neurology and Epidemiology (M.S.V.E.), and Division of Cardiology (M.R.D.T., S.H.), Columbia University, NY; Neurology Service, Centre Hospitalier Universitaire Vaudois (P.M.), Switzerland; Department of Cardiology (B.M.), Swiss Cardiovascular Center, Inselspital, University of Bern, Switzerland; and Department of Neurology (A.J.F.), Case Western Reserve University, Cleveland, OH.
authors.forename: Mitchell S V
authors.initials: MS
authors.lastname: Elkind
authors.affiliation: From the Department of Neurology (D.E.T., D.M.K.), and Predictive Analytics and Comparative Effectiveness Center, Institute for Clinical Research and Health Policy Studies (R.R., J.S.L., D.M.K.), Tufts Medical Center/Tufts University School of Medicine, Boston, MA; Department of Neurology, University of Duisburg-Essen (C.W.), Germany; Neurology Department at the Hospital Universitari Doctor Josep Trueta Institut d'Investigació Biomèdica de Girona (J.S.), Spain; Department of Neurology, Inselspital (H.P.M., M.-L.M.), University of Bern; Division of Neurology at the Triemli Municipal Hospital (K.N.), Zurich, Switzerland; Department of Public Health and Primary Care (E.D.A.), Cambridge University, UK; Departments of Neurology and Epidemiology (M.S.V.E.), and Division of Cardiology (M.R.D.T., S.H.), Columbia University, NY; Neurology Service, Centre Hospitalier Universitaire Vaudois (P.M.), Switzerland; Department of Cardiology (B.M.), Swiss Cardiovascular Center, Inselspital, University of Bern, Switzerland; and Department of Neurology (A.J.F.), Case Western Reserve University, Cleveland, OH.
authors.forename: Marco R
authors.initials: MR
authors.lastname: Di Tullio
authors.affiliation: From the Department of Neurology (D.E.T., D.M.K.), and Predictive Analytics and Comparative Effectiveness Center, Institute for Clinical Research and Health Policy Studies (R.R., J.S.L., D.M.K.), Tufts Medical Center/Tufts University School of Medicine, Boston, MA; Department of Neurology, University of Duisburg-Essen (C.W.), Germany; Neurology Department at the Hospital Universitari Doctor Josep Trueta Institut d'Investigació Biomèdica de Girona (J.S.), Spain; Department of Neurology, Inselspital (H.P.M., M.-L.M.), University of Bern; Division of Neurology at the Triemli Municipal Hospital (K.N.), Zurich, Switzerland; Department of Public Health and Primary Care (E.D.A.), Cambridge University, UK; Departments of Neurology and Epidemiology (M.S.V.E.), and Division of Cardiology (M.R.D.T., S.H.), Columbia University, NY; Neurology Service, Centre Hospitalier Universitaire Vaudois (P.M.), Switzerland; Department of Cardiology (B.M.), Swiss Cardiovascular Center, Inselspital, University of Bern, Switzerland; and Department of Neurology (A.J.F.), Case Western Reserve University, Cleveland, OH.
authors.forename: Shunichi
authors.initials: S
authors.lastname: Homma
authors.affiliation: From the Department of Neurology (D.E.T., D.M.K.), and Predictive Analytics and Comparative Effectiveness Center, Institute for Clinical Research and Health Policy Studies (R.R., J.S.L., D.M.K.), Tufts Medical Center/Tufts University School of Medicine, Boston, MA; Department of Neurology, University of Duisburg-Essen (C.W.), Germany; Neurology Department at the Hospital Universitari Doctor Josep Trueta Institut d'Investigació Biomèdica de Girona (J.S.), Spain; Department of Neurology, Inselspital (H.P.M., M.-L.M.), University of Bern; Division of Neurology at the Triemli Municipal Hospital (K.N.), Zurich, Switzerland; Department of Public Health and Primary Care (E.D.A.), Cambridge University, UK; Departments of Neurology and Epidemiology (M.S.V.E.), and Division of Cardiology (M.R.D.T., S.H.), Columbia University, NY; Neurology Service, Centre Hospitalier Universitaire Vaudois (P.M.), Switzerland; Department of Cardiology (B.M.), Swiss Cardiovascular Center, Inselspital, University of Bern, Switzerland; and Department of Neurology (A.J.F.), Case Western Reserve University, Cleveland, OH.
authors.forename: Patrik
authors.initials: P
authors.lastname: Michel
authors.affiliation: From the Department of Neurology (D.E.T., D.M.K.), and Predictive Analytics and Comparative Effectiveness Center, Institute for Clinical Research and Health Policy Studies (R.R., J.S.L., D.M.K.), Tufts Medical Center/Tufts University School of Medicine, Boston, MA; Department of Neurology, University of Duisburg-Essen (C.W.), Germany; Neurology Department at the Hospital Universitari Doctor Josep Trueta Institut d'Investigació Biomèdica de Girona (J.S.), Spain; Department of Neurology, Inselspital (H.P.M., M.-L.M.), University of Bern; Division of Neurology at the Triemli Municipal Hospital (K.N.), Zurich, Switzerland; Department of Public Health and Primary Care (E.D.A.), Cambridge University, UK; Departments of Neurology and Epidemiology (M.S.V.E.), and Division of Cardiology (M.R.D.T., S.H.), Columbia University, NY; Neurology Service, Centre Hospitalier Universitaire Vaudois (P.M.), Switzerland; Department of Cardiology (B.M.), Swiss Cardiovascular Center, Inselspital, University of Bern, Switzerland; and Department of Neurology (A.J.F.), Case Western Reserve University, Cleveland, OH.
authors.forename: Bernhard
authors.initials: B
authors.lastname: Meier
authors.affiliation: From the Department of Neurology (D.E.T., D.M.K.), and Predictive Analytics and Comparative Effectiveness Center, Institute for Clinical Research and Health Policy Studies (R.R., J.S.L., D.M.K.), Tufts Medical Center/Tufts University School of Medicine, Boston, MA; Department of Neurology, University of Duisburg-Essen (C.W.), Germany; Neurology Department at the Hospital Universitari Doctor Josep Trueta Institut d'Investigació Biomèdica de Girona (J.S.), Spain; Department of Neurology, Inselspital (H.P.M., M.-L.M.), University of Bern; Division of Neurology at the Triemli Municipal Hospital (K.N.), Zurich, Switzerland; Department of Public Health and Primary Care (E.D.A.), Cambridge University, UK; Departments of Neurology and Epidemiology (M.S.V.E.), and Division of Cardiology (M.R.D.T., S.H.), Columbia University, NY; Neurology Service, Centre Hospitalier Universitaire Vaudois (P.M.), Switzerland; Department of Cardiology (B.M.), Swiss Cardiovascular Center, Inselspital, University of Bern, Switzerland; and Department of Neurology (A.J.F.), Case Western Reserve University, Cleveland, OH.
authors.forename: Anthony J
authors.initials: AJ
authors.lastname: Furlan
authors.affiliation: From the Department of Neurology (D.E.T., D.M.K.), and Predictive Analytics and Comparative Effectiveness Center, Institute for Clinical Research and Health Policy Studies (R.R., J.S.L., D.M.K.), Tufts Medical Center/Tufts University School of Medicine, Boston, MA; Department of Neurology, University of Duisburg-Essen (C.W.), Germany; Neurology Department at the Hospital Universitari Doctor Josep Trueta Institut d'Investigació Biomèdica de Girona (J.S.), Spain; Department of Neurology, Inselspital (H.P.M., M.-L.M.), University of Bern; Division of Neurology at the Triemli Municipal Hospital (K.N.), Zurich, Switzerland; Department of Public Health and Primary Care (E.D.A.), Cambridge University, UK; Departments of Neurology and Epidemiology (M.S.V.E.), and Division of Cardiology (M.R.D.T., S.H.), Columbia University, NY; Neurology Service, Centre Hospitalier Universitaire Vaudois (P.M.), Switzerland; Department of Cardiology (B.M.), Swiss Cardiovascular Center, Inselspital, University of Bern, Switzerland; and Department of Neurology (A.J.F.), Case Western Reserve University, Cleveland, OH.
authors.forename: Jennifer S
authors.initials: JS
authors.lastname: Lutz
authors.affiliation: From the Department of Neurology (D.E.T., D.M.K.), and Predictive Analytics and Comparative Effectiveness Center, Institute for Clinical Research and Health Policy Studies (R.R., J.S.L., D.M.K.), Tufts Medical Center/Tufts University School of Medicine, Boston, MA; Department of Neurology, University of Duisburg-Essen (C.W.), Germany; Neurology Department at the Hospital Universitari Doctor Josep Trueta Institut d'Investigació Biomèdica de Girona (J.S.), Spain; Department of Neurology, Inselspital (H.P.M., M.-L.M.), University of Bern; Division of Neurology at the Triemli Municipal Hospital (K.N.), Zurich, Switzerland; Department of Public Health and Primary Care (E.D.A.), Cambridge University, UK; Departments of Neurology and Epidemiology (M.S.V.E.), and Division of Cardiology (M.R.D.T., S.H.), Columbia University, NY; Neurology Service, Centre Hospitalier Universitaire Vaudois (P.M.), Switzerland; Department of Cardiology (B.M.), Swiss Cardiovascular Center, Inselspital, University of Bern, Switzerland; and Department of Neurology (A.J.F.), Case Western Reserve University, Cleveland, OH.
authors.forename: David M
authors.initials: DM
authors.lastname: Kent
mesh_terms: D000328:Adult; D000368:Aged; D002755:Choice Behavior; D015331:Cohort Studies; D016208:Databases, Factual / Q000639:trends; D005260:Female; D005343:Fibrinolytic Agents / Q000627:therapeutic use*; D054092:Foramen Ovale, Patent / Q000188:drug therapy* / Q000453:epidemiology*; D006801:Humans; D008297:Male; D008875:Middle Aged; D020521:Stroke / Q000188:drug therapy* / Q000453:epidemiology*
chemical_list: D005343:Fibrinolytic Agents