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Long-term antithrombotic treatment in intracranial hemorrhage survivors with atrial fibrillation

  1. Roland Veltkamp, MD
  1. From the Division of Brain Sciences (E.K., A.D.G., R.V.), Department of Stroke Medicine, and Department of Primary Care and Public Health (F.T.F.), Imperial College, London, UK; Aalborg Thrombosis Research Unit (P.B.N., G.Y.H.L.), Department of Clinical Medicine, Faculty of Medicine, Aalborg University, Denmark; Institute of Cardiovascular Sciences (G.Y.H.L.), University of Birmingham, UK; Department of Neurology (J.B.K., H.B.H.), University of Erlangen-Nuremberg, Erlangen, Germany; Institute for Clinical Evaluative Sciences (J.F.), Toronto; Thrombosis and Atherosclerosis Research Institute (S.S.), Department of Medicine, McMaster University, Hamilton, Ontario, Canada; Stroke Unit (J.M.-F.), Department of Neurology, Hospital de la Santa Creu i Sant Pau, IIB-Sant Pau, Barcelona, Spain; Department of Neurology and Neurosurgery (C.S.G.), Brain Center Rudolf Magnus, University Medical Center Utrecht, the Netherlands; Department of Neurology (A.V., A.B.), Massachusetts General Hospital, Harvard Medical School, Boston; Thrombosis Center (D.P.), Careggi Hospital, Florence, Italy; Department of Neurology (C.W.), University Hospital of Duisburg-Essen, Essen; Clinical Trial Center Würzburg (U.M., P.H.), University Hospital Würzburg; and Institute of Clinical Epidemiology and Biometry (P.H.), Comprehensive Heart Failure Center, University Würzburg, Germany.
  1. Correspondence to Dr. Veltkamp: r.veltkamp{at}imperial.ac.uk
Scientific Advisory Boards:

  1. NONE

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Employment, Commercial Entity:

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Other Activities:

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Clinical Procedures or Imaging Studies:

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Research Support, Commercial Entities:

  1. NONE

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  1. NONE

Research Support, Academic Entities:

  1. NONE

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Stock/Stock Options/Board of Directors Compensation:

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License Fee Payments, Technology or Inventions:

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Royalty Payments, Technology or Inventions:

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  1. NONE

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Gifts:

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Funding for Travel or Speaker Honoraria:

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  1. NONE

Employment, Commercial Entity:

  1. NONE

Consultancies:

  1. NONE

Speakers' Bureaus:

  1. NONE

Other Activities:

  1. NONE

Clinical Procedures or Imaging Studies:

  1. NONE

Research Support, Commercial Entities:

  1. NONE

Research Support, Government Entities:

  1. NONE

Research Support, Academic Entities:

  1. NONE

Research Support, Foundations and Societies:

  1. NONE

Stock/Stock Options/Board of Directors Compensation:

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License Fee Payments, Technology or Inventions:

  1. NONE

Royalty Payments, Technology or Inventions:

  1. NONE

Stock/Stock Options, Research Sponsor:

  1. NONE

Stock/Stock Options, Medical Equipment & Materials:

  1. NONE

Legal Proceedings:

  1. NONE

Scientific Advisory Boards:

  1. NONE

Gifts:

  1. NONE

Funding for travel or speaker honoraria:

  1. Bayer Pharma AG BMS/Pfizer

Editorial Boards:

  1. NONE

Patents:

  1. NONE

Publishing Royalties:

  1. NONE

Employment, Commercial Entity:

  1. NONE

Consultancies:

  1. Bayer Pharma AG BMS/Pfizer

Speakers' Bureaus:

  1. BMS/Pfizer boehringer ingelheim

Other Activities:

  1. NONE

Clinical Procedures or Imaging Studies:

  1. NONE

Research Support, Commercial Entities:

  1. NONE

Research Support, Government Entities:

  1. NONE

Research Support, Academic Entities:

  1. NONE

Research Support, Foundations and Societies:

  1. NONE

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  1. NONE

License Fee Payments, Technology or Inventions:

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  1. NONE

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Gifts:

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Funding for Travel or Speaker Honoraria:

  1. NONE

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  1. NONE

Employment, Commercial Entity:

  1. NONE

Consultancies:

  1. NONE

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  1. NONE

Other Activities:

  1. NONE

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  1. NONE

Research Support, Commercial Entities:

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  1. NONE

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  1. NONE

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  1. NONE

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Gifts:

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Funding for Travel or Speaker Honoraria:

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Editorial Boards:

  1. Editor in Chief for Thrombosis & Haemostasis, Guest Editor for Circulation, Associate Editor for Europace

Patents:

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  1. NONE

Employment, Commercial Entity:

  1. NONE

Consultancies:

  1. Consultant for Bayer/Janssen, BMS/Pfizer, Biotronik, Medtronic, Boehringer Ingelheim, Microlife and Daiichi-Sankyo. No fees are received personally.

Speakers' Bureaus:

  1. Speakers bureau for Bayer, BMS/Pfizer, Boehringer Ingelheim, Roche and Sanofi Aventis. No fees are received personally.

Other Activities:

  1. NONE

Clinical Procedures or Imaging Studies:

  1. NONE

Research Support, Commercial Entities:

  1. My department has received support from Bayer, BMS/Pfizer, and Boehringer Ingelheim

Research Support, Government Entities:

  1. NONE

Research Support, Academic Entities:

  1. British Heart Foundation, NIHR

Research Support, Foundations and Societies:

  1. NONE

Stock/Stock Options/Board of Directors Compensation:

  1. NONE

License Fee Payments, Technology or Inventions:

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  1. NONE

Gifts:

  1. NONE

Funding for travel or speaker honoraria:

  1. Speaker honoraria - Sanofi,Boehringer Ingelheim

Editorial Boards:

  1. NONE

Patents:

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  1. NONE

Employment, Commercial Entity:

  1. NONE

Consultancies:

  1. NONE

Speakers' Bureaus:

  1. NONE

Other Activities:

  1. NONE

Clinical Procedures or Imaging Studies:

  1. NONE

Research Support, Commercial Entities:

  1. Research grant unrelated to the manuscript by Medtronic

Research Support, Government Entities:

  1. NONE

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  1. NONE

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Stock/Stock Options, Research Sponsor:

  1. NONE

Stock/Stock Options, Medical Equipment & Materials:

  1. NONE

Legal Proceedings:

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Scientific Advisory Boards:

  1. (1) Advisory Board fees from Boehringer Ingelheim (2) Advisory Board fees from Medtronic

Gifts:

  1. NONE

Funding for travel or speaker honoraria:

  1. (1) Travel honoraria from Boehringer Ingelheim

Editorial Boards:

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Patents:

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Employment, Commercial Entity:

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Other Activities:

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Clinical Procedures or Imaging Studies:

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Scientific Advisory Boards:

  1. Data safety monitoring board for non-profit entity (NIH)

Gifts:

  1. NONE

Funding for Travel or Speaker Honoraria:

  1. NONE

Editorial Boards:

  1. Section editor for Thrombosis and Haemostasis, Associate editor for Seminars in Thrombosis and Hemostasis and for Journal of Internal Medicine

Patents:

  1. NONE

Publishing Royalties:

  1. Hemostasis and Thrombosis - basic principles and clinical practice 2015

Employment, Commercial Entity:

  1. NONE

Consultancies:

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Speakers' Bureaus:

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Other Activities:

  1. NONE

Clinical Procedures or Imaging Studies:

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Research Support, Commercial Entities:

  1. Boehringer Ingelheim, Baxter, Octapharma

Research Support, Government Entities:

  1. NONE

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  1. NONE

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Other Activities:

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Research Support, Commercial Entities:

  1. NONE

Research Support, Government Entities:

  1. Instituto de Salus Carlos III, RETICS INVICTUS PLUS RD16/0019/0010, Principal Investigador, 2016-2020 Instituto de Salus Carlos III, Fondo de Investigaciones Sanitarias PI15/00884, Principal Investigator

Research Support, Academic Entities:

  1. NONE

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Research Support, Commercial Entities:

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Scientific Advisory Boards:

  1. Has served on a Data safety monitoring board for Roche Pharmaceuticals.

Gifts:

  1. NONE

Funding for Travel or Speaker Honoraria:

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Editorial Boards:

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Patents:

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Publishing Royalties:

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Employment, Commercial Entity:

  1. NONE

Consultancies:

  1. Dr. Viswanathan has served as consultant for Athena Diagnostics.

Speakers' Bureaus:

  1. NONE

Other Activities:

  1. NONE

Clinical Procedures or Imaging Studies:

  1. NONE

Research Support, Commercial Entities:

  1. NONE

Research Support, Government Entities:

  1. (1) NIA 2P50AG005134-268382, investigator; (2) 1K23AG028726-01A2, investigator (3) 1R01AG047975-02, investigator

Research Support, Academic Entities:

  1. NONE

Research Support, Foundations and Societies:

  1. NONE

Stock/Stock Options/Board of Directors Compensation:

  1. NONE

License Fee Payments, Technology or Inventions:

  1. NONE

Royalty Payments, Technology or Inventions:

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Stock/Stock Options, Research Sponsor:

  1. NONE

Stock/Stock Options, Medical Equipment & Materials:

  1. NONE

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Gifts:

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Funding for Travel or Speaker Honoraria:

  1. NONE

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Employment, Commercial Entity:

  1. NONE

Consultancies:

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  1. NONE

Other Activities:

  1. NONE

Clinical Procedures or Imaging Studies:

  1. NONE

Research Support, Commercial Entities:

  1. NONE

Research Support, Government Entities:

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Research Support, Foundations and Societies:

  1. NONE

Stock/Stock Options/Board of Directors Compensation:

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Gifts:

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Funding for Travel or Speaker Honoraria:

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Publishing Royalties:

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Employment, Commercial Entity:

  1. NONE

Consultancies:

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  1. NONE

Other Activities:

  1. NONE

Clinical Procedures or Imaging Studies:

  1. NONE

Research Support, Commercial Entities:

  1. NONE

Research Support, Government Entities:

  1. NONE

Research Support, Academic Entities:

  1. NONE

Research Support, Foundations and Societies:

  1. NONE

Stock/Stock Options/Board of Directors Compensation:

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  1. NONE

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  1. NONE

Stock/Stock Options, Research Sponsor:

  1. NONE

Stock/Stock Options, Medical Equipment & Materials:

  1. NONE

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  1. NONE

Scientific Advisory Boards:

  1. (1) Bayer Schering (2) Bristol-Myers Squib (3) AMGEN

Gifts:

  1. NONE

Funding for travel or speaker honoraria:

  1. (1) Deutsche Gesellschaft f?r Neurologie, funding for travel (2) Biogen Idec, speaker honoraria (3) Boehringer Ingelheim, speaker honoraria (4) Bayer Schering, speaker honoraria (5) AMGEN, speaker honoraria

Editorial Boards:

  1. (1) Cerebrovascular Diseases, editorial board member, 2008-2013(2) Stroke News, editorial office 2006- ongoing

Patents:

  1. NONE

Publishing Royalties:

  1. NONE

Employment, Commercial Entity:

  1. Consultant, University hospital Essen

Consultancies:

  1. NONE

Speakers' Bureaus:

  1. (1) Sanofi Aventis (2) Boehringer Ingelheim

Other activities:

  1. participation in clinical trials by (1) Brainsgate, (2) D-Pharm (3) PhotoThera (4) Portola (5) Pierre Fabre

Clinical Procedures or Imaging Studies:

  1. NONE

Research Support, Commercial Entities:

  1. (1) Johnson & Johnson (2) Boehringer Ingelheim

Research Support, Government Entities:

  1. (1) German Research Council, 2010-2015, WE 2858/3-1

Research Support, Academic Entities:

  1. NONE

Research Support, Foundations and Societies:

  1. NONE

Stock/Stock Options/Board of Directors Compensation:

  1. NONE

License Fee Payments, Technology or Inventions:

  1. NONE

Royalty Payments, Technology or Inventions:

  1. NONE

Stock/Stock Options, Research Sponsor:

  1. NONE

Stock/Stock Options, Medical Equipment & Materials:

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Gifts:

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Funding for Travel or Speaker Honoraria:

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Patents:

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Publishing Royalties:

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Employment, Commercial Entity:

  1. NONE

Consultancies:

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Speakers' Bureaus:

  1. NONE

Other Activities:

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Clinical Procedures or Imaging Studies:

  1. NONE

Research Support, Commercial Entities:

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Research Support, Government Entities:

  1. NONE

Research Support, Academic Entities:

  1. NONE

Research Support, Foundations and Societies:

  1. NONE

Stock/Stock Options/Board of Directors Compensation:

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License Fee Payments, Technology or Inventions:

  1. NONE

Royalty Payments, Technology or Inventions:

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Stock/Stock Options, Research Sponsor:

  1. NONE

Stock/Stock Options, Medical Equipment & Materials:

  1. NONE

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Scientific Advisory Boards:

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Gifts:

  1. NONE

Funding for Travel or Speaker Honoraria:

  1. NONE

Editorial Boards:

  1. NONE

Patents:

  1. NONE

Publishing Royalties:

  1. NONE

Employment, Commercial Entity:

  1. NONE

Consultancies:

  1. NONE

Speakers' Bureaus:

  1. NONE

Other Activities:

  1. NONE

Clinical Procedures or Imaging Studies:

  1. NONE

Research Support, Commercial Entities:

  1. NONE

Research Support, Government Entities:

  1. 1) Federal Ministry of Education and Research (BMBF), within the Center for Stroke Research (2008-2011), within the Comprehensive Heart Failure Center W?rzburg (2012-2020) 2) European Union, European Implementation Score Project, 2009-2013

Research Support, Academic Entities:

  1. 1) Charit? - Universit?tsmedizin Berlin 2) University Hospital W?rzburg 3) Charit? ? Universit?tsmedizin Berlin (within Mondafis; Mondafis is supported by an unrestricted research grant to the Charit? from Bayer) 4) University G?ttingen (within FIND-AF randomized; FIND-AF randomized is supported by an unrestricted research grant to the University G?ttingen from Boehringer-Ingelheim) 5) University Hospital Heidelberg (within RASUNOA-prime; RASUNOA-prime is supported by an unrestricted research grant to the University Hospital Heidelberg from Bayer, BMS, Boehringer-Ingelheim, Daiichi Sankyo)

Research Support, Foundations and Societies:

  1. 1) Berlin Chambers of Physicians 2) German Parkinson Society 3) Robert Koch Institute 4) German Heart Foundation

Stock/Stock Options/Board of Directors Compensation:

  1. NONE

License Fee Payments, Technology or Inventions:

  1. NONE

Royalty Payments, Technology or Inventions:

  1. NONE

Stock/Stock Options, Research Sponsor:

  1. NONE

Stock/Stock Options, Medical Equipment & Materials:

  1. NONE

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  1. NONE

Scientific Advisory Boards:

  1. (1) Bayer (2) Boehringer-Ingelheim (3) BMS/Pfizer (4) Daiichi Sankyo (5) Amgen (6) Sanofi (7) Biogen (8) AZT Therapies

Gifts:

  1. NONE

Funding for travel or speaker honoraria:

  1. (1) Bayer (2) Boehringer Ingelheim (3) BMS/Pfizer (4) Sanofi Aventis (5) Roche (6) Apoplexmedicaltechnologies (7) St. Jude Medical (8) Daiichi Sankyo (all speaker honoraria)

Editorial Boards:

  1. Stroke, Cerbrovascular disorders (editorial board member)

Patents:

  1. NONE

Publishing Royalties:

  1. NONE

Employment, Commercial Entity:

  1. NONE

Consultancies:

  1. (1) Morphosys (2) Daiichi Sankyo (3) Biogen

Speakers' Bureaus:

  1. NONE

Other Activities:

  1. NONE

Clinical Procedures or Imaging Studies:

  1. NONE

Research Support, Commercial Entities:

  1. 1) Bayer (2) Boehringer Ingelheim (3) BMS/Pfizer (4) Daiichi Sanky (5)Biogen

Research Support, Government Entities:

  1. Deutsche Forschungsgemeinschaft DFG VE 196/3-1 (unrelated)

Research Support, Academic Entities:

  1. NONE

Research Support, Foundations and Societies:

  1. Else Kr?ner Fresenius Stiftung (unrelated)

Stock/Stock Options/Board of Directors Compensation:

  1. NONE

License Fee Payments, Technology or Inventions:

  1. NONE

Royalty Payments, Technology or Inventions:

  1. NONE

Stock/Stock Options, Research Sponsor:

  1. NONE

Stock/Stock Options, Medical Equipment & Materials:

  1. Bayer

Legal Proceedings:

  1. NONE

Abstract

Objective: To perform a systematic review and meta-analysis of studies reporting recurrent intracranial hemorrhage (ICH) and ischemic stroke (IS) in ICH survivors with atrial fibrillation (AF) during long-term follow-up.

Methods: A comprehensive literature search including MEDLINE, EMBASE, Cochrane library, clinical trials registry was performed following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statement. We considered studies capturing outcome events (ICH recurrence and IS) for ≥3 months and treatment exposure to vitamin K antagonists (VKAs), antiplatelet agents (APAs), or no antithrombotic medication (no-ATM). Corresponding authors provided aggregate data for IS and ICH recurrence rate between 6 weeks after the event and 1 year of follow-up for each treatment exposure. Meta-analyses of pooled rate ratios (RRs) were conducted with the inverse variance method.

Results: Seventeen articles met inclusion criteria. Seven observational studies enrolling 2,452 patients were included in the meta-analysis. Pooled RR estimates for IS were lower for VKAs compared to APAs (RR = 0.45, 95% confidence interval [CI] 0.27–0.74, p = 0.002) and no-ATM (RR = 0.47, 95% CI 0.29–0.77, p = 0.002). Pooled RR estimates for ICH recurrence were not significantly increased across treatment groups (VKA vs APA: RR = 1.34, 95% CI 0.79–2.30, p = 0.28; VKA vs no-ATM: RR = 0.93, 95% CI 0.45–1.90, p = 0.84).

Conclusions: In observational studies, anticoagulation with VKA is associated with a lower rate of IS than APA or no-ATM without increasing ICH recurrence significantly. A randomized controlled trial is needed to determine the net clinical benefit of anticoagulation in ICH survivors with AF.

Footnotes

  • ↵* These authors contributed equally to this work.

  • Received December 29, 2016.
  • Accepted in final form May 23, 2017.
  1. Published online before print July 19, 2017, doi: 10.1212/WNL.0000000000004235 Neurology 10.1212/WNL.0000000000004235
  1. » Abstract
  2. Full Text (PDF)
  3. Data Supplement

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