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Ischaemic stroke on anticoagulation therapy and early recurrence in acute cardioembolic stroke: the IAC study
  1. Shadi Yaghi1,
  2. Nils Henninger2,3,
  3. James A Giles4,
  4. Christopher Leon Guerrero5,
  5. Eva Mistry6,
  6. Ava L Liberman7,
  7. Daniyal Asad8,
  8. Angela Liu4,
  9. Muhammad Nagy2,
  10. Ashutosh Kaushal9,
  11. Idrees Azher6,9,
  12. Brian Mac Grory9,
  13. Hiba Fakhri6,
  14. Kiersten Brown Espaillat6,
  15. Hemanth Pasupuleti10,
  16. Heather Martin10,
  17. Jose Tan10,
  18. Manivannan Veerasamy10,
  19. Charles Esenwa7,
  20. Natalie Cheng7,
  21. Khadean Moncrieffe7,
  22. Iman Moeini-Naghani5,
  23. Mithilesh Siddu5,
  24. Erica Scher11,
  25. Tushar Trivedi11,
  26. Karen L Furie9,
  27. Salah G Keyrouz4,
  28. Amre Nouh8,
  29. Adam de Havenon12,
  30. Muhib Khan10,13,
  31. Eric E Smith14,
  32. M Edip Gurol15,16
  1. 1 Dpeartment of Neurology, Brown University, Providence, Rhode Island, USA
  2. 2 Neurology, University of Massachusetts Medical School, Worcester, Massachusetts, USA
  3. 3 Department of Psychiatry, University of Massachusetts, Worcester, Massachusetts, USA
  4. 4 Neurology, Washington University in Saint Louis, St Louis, Missouri, USA
  5. 5 The George Washington University School of Medicine and Health Sciences, Washington, District of Columbia, USA
  6. 6 Neurology, Vanderbilt University, Nashville, Tennessee, USA
  7. 7 Neurology, Montefiore Hospital and Medical Center, Bronx, New York, USA
  8. 8 Neurology, Hartford Hospital, Hartford, Connecticut, USA
  9. 9 Neurology, Brown University Warren Alpert Medical School, Providence, Rhode Island, USA
  10. 10 Neuroscience Institute, Spectrum Health, Grand Rapids, Michigan, USA
  11. 11 Neurology, NYU Langone Health, New York, New York, USA
  12. 12 Neurology, University of Utah Health Hospitals and Clinics, Salt Lake City, Utah, USA
  13. 13 Neurology, Michigan State University College of Human Medicine, Grand Rapids, Michigan, USA
  14. 14 Hotchkiss Brain Institute, University of Calgary, Calgary, Alberta, Canada
  15. 15 Neurology, Massachusetts General Hospital, Boston, Massachusetts, USA
  16. 16 Neurology, Harvard Medical School, Boston, Massachusetts, USA
  1. Correspondence to Dr Shadi Yaghi, Neurology, Columbia University Medical Center, New York, New York, USA; shadiyaghi{at}


Background and purpose A subset of ischaemic stroke patients with atrial fibrillation (AF) have ischaemic stroke despite anticoagulation. We sought to determine the association between prestroke anticoagulant therapy and recurrent ischaemic events and symptomatic intracranial haemorrhage (sICH).

Methods We included consecutive patients with acute ischaemic stroke and AF from the Initiation of Anticoagulation after Cardioembolic stroke (IAC) study from eight comprehensive stroke centres in the USA. We compared recurrent ischaemic events and delayed sICH risk using adjusted Cox regression analyses between patients who were prescribed anticoagulation (ACp) versus patients who were naïve to anticoagulation therapy prior to the ischaemic stroke (anticoagulation naïve).

Results Among 2084 patients in IAC, 1518 had prior anticoagulation status recorded and were followed for 90 days. In adjusted Cox hazard models, ACp was associated with some evidence of a higher risk higher risk of 90-day recurrent ischaemic events only in the fully adjusted model (adjusted HR 1.50, 95% CI 0.99 to 2.28, p=0.058) but not increased risk of 90-day sICH (adjusted HR 1.08, 95% CI 0.46 to 2.51, p=0.862). In addition, switching anticoagulation class was not associated with reduced risk of recurrent ischaemic events (adjusted HR 0.41, 95% CI 0.12 to 1.33, p=0.136) nor sICH (adjusted HR 1.47, 95% CI 0.29 to 7.50, p=0.641).

Conclusion AF patients with ischaemic stroke despite anticoagulation may have higher recurrent ischaemic event risk compared with anticoagulation-naïve patients. This suggests differing underlying pathomechanisms requiring different stroke prevention measures and identifying these mechanisms may improve secondary prevention strategies.

Data availability statement

Data are available on reasonable request.

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Data availability statement

Data are available on reasonable request.

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  • Contributors SY, NH, AdH: Study concept design, drafting manuscript, and statistical analysis. JAG, CRLG, EM, ALL, DA, AL, MN, AK, IA, BMG, HF, KBE, HP, HM, JT, MV, CE, NC, KM, IM-N, MS, KLF, SGK, AN and MK: data collection and manuscript revisions. ESc and TT: data management and manuscript revision. ESm and MEG: study concept and design and manuscript revision.

  • Funding The authors have not declared a specific grant for this research from any funding agency in the public, commercial or not-for-profit sectors.

  • Competing interests SY has a non-funded research collaboration with Medtronic. MEG reports grants from AVID (Eli Lilly), grants from Boston Scientific, and grants from Pfizer outside the submitted work. NH reports grants from NINDS during the conduct of the study; grants from NICHD of the NIH, grants from NINDS of the NIH, grants from CDMRP of the DoD, and personal fees from Astrocyte Pharmaceuticals outside the submitted work. EM reports grants from NIH/NINDS outside the submitted work. AdH reports research support from AMAG and Regeneron.

  • Provenance and peer review Not commissioned; externally peer reviewed.

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