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November 18, 2014; 83 (21) Article

Determinants of antithrombotic choice for patent foramen ovale in cryptogenic stroke

David E. Thaler, Robin Ruthazer, Christian Weimar, Joaquín Serena, Heinrich P. Mattle, Krassen Nedeltchev, Marie-Luise Mono, Emanuele Di Angelantonio, Mitchell S.V. Elkind, Marco R. Di Tullio, Shunichi Homma, Patrik Michel, Bernhard Meier, Anthony J. Furlan, Jennifer S. Lutz, David M. Kent
First published October 22, 2014, DOI: https://doi.org/10.1212/WNL.0000000000001007
David E. Thaler
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.
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Robin Ruthazer
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.
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Christian Weimar
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.
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Joaquín Serena
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.
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Heinrich P. Mattle
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.
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Krassen Nedeltchev
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.
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Marie-Luise Mono
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.
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Emanuele Di Angelantonio
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.
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Mitchell S.V. Elkind
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.
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Marco R. Di Tullio
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.
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Shunichi Homma
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.
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Patrik Michel
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.
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Bernhard Meier
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.
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Anthony J. Furlan
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.
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Jennifer S. Lutz
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.
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David M. Kent
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.
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Citation
Determinants of antithrombotic choice for patent foramen ovale in cryptogenic stroke
David E. Thaler, Robin Ruthazer, Christian Weimar, Joaquín Serena, Heinrich P. Mattle, Krassen Nedeltchev, Marie-Luise Mono, Emanuele Di Angelantonio, Mitchell S.V. Elkind, Marco R. Di Tullio, Shunichi Homma, Patrik Michel, Bernhard Meier, Anthony J. Furlan, Jennifer S. Lutz, David M. Kent
Neurology Nov 2014, 83 (21) 1954-1957; DOI: 10.1212/WNL.0000000000001007

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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.

Conclusion: 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.

GLOSSARY

CS=
cryptogenic stroke;
PFO=
patent foramen ovale;
PICSS=
PFO in Cryptogenic Stroke Study;
RoPE=
Risk of Paradoxical Embolism

Footnotes

  • Go to Neurology.org for full disclosures. Funding information and disclosures deemed relevant by the authors, if any, are provided at the end of the article.

  • Supplemental data at Neurology.org

  • Received April 17, 2014.
  • Accepted in final form August 22, 2014.
  • © 2014 American Academy of Neurology
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Neurology: 101 (5)

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