J Neurol Neurosurg Psychiatry 83:537-540 doi:10.1136/jnnp-2011-301794
  • Cerebrovascular disease
  • Research paper

Thrombolytic therapy for ischaemic stroke in patients using warfarin: a systematic review and meta-analysis

  1. Maarten Uyttenboogaart1
  1. 1Department of Neurology, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands
  2. 2Department of Neurology, Universitair Ziekenhuis Brussel, Center for Neurosciences, Vrije Universiteit Brussel, Brussel, Belgium
  3. 3Department of Clinical Neurosciences, University of Calgary, Foothills Hospital, Calgary, Alberta, Canada
  1. Correspondence to Maarten Uyttenboogaart, Department of Neurology, University Medical Center Groningen, University of Groningen, Hanzeplein 1, Groningen 9713 GZ, The Netherlands; m.uyttenboogaart{at}
  1. Contributors IM performed the systematic review, extracted the data from the studies for the meta-analysis and wrote the first draft. GJL critically appraised the draft for intellectual content and supervised the systematic review. MK and JDeK critically appraised the draft for intellectual content. MU had the idea of performing this review/meta-analysis, extracted data from the studies and critically appraised the draft for intellectual content.

  • Received 7 November 2011
  • Revised 23 January 2012
  • Accepted 25 January 2012
  • Published Online First 29 February 2012


Background It is uncertain whether thrombolytic therapy is safe in patients with acute ischaemic stroke who are treated with warfarin and have a subtherapeutic international normalised ratio (INR) at stroke onset.

Methods The authors performed a systematic review of the literature and included studies that assessed the relation between prior warfarin use with subtherapeutic INR and outcome after intravenous or intra-arterial thrombolytic therapy in acute ischaemic stroke. Outcome measures were symptomatic intracranial haemorrhage (SICH), modified Rankin scale score 0–2 and mortality. Second, the authors performed a meta-analysis of the included studies.

Results Seven studies with 3631 patients were included. 240 (6.6%) patients used warfarin before stroke onset. The risk of SICH was increased in the warfarin group (OR 2.6; 95% CI 1.1 to 5.9. p=0.02). There was no significant difference, however, in functional outcome (OR 0.9; 95% CI 0.6 to 1.2, p=0.32) or death from all causes (OR 1.2; 95% CI 0.9 to 1.8).

Discussion The risk of SICH after thrombolytic therapy is increased in patients using warfarin with subtherapeutic INR levels. The authors found no evidence of an increase in death from all causes or worsening of functional outcome in warfarin treated patients.


  • Funding This study was funded by the University Medical Center Groningen, The Netherlands.

  • Competing interests None.

  • Ethics approval The ethics approval was provided by systematic review and meta-analysis of previously published studies.

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

  • Data sharing statement This study is a systematic review and meta-analysis of published studies. We did not use any unpublished data for this study.

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