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Research paper
Outcome of intracerebral haemorrhage related to non-vitamin K antagonists oral anticoagulants versus vitamin K antagonists: a comprehensive systematic review and meta-analysis
  1. Gregoire Boulouis1,
  2. Andrea Morotti2,
  3. Marco Pasi3,4,
  4. Joshua N Goldstein3,4,5,
  5. M Edip Gurol3,4,
  6. Andreas Charidimou3,4
  1. 1 Department of Neuroradiology, Université Paris-Descartes, Centre Hospitalier Sainte Anne, Paris, Ile de France, France
  2. 2 Department of Emergency Neurology, Stroke Unit, C. Mondino National Neurological Institute, Pavia, Italy
  3. 3 Department of Hemorrhagic Stroke Research Group, Massachusetts General Hospital, Boston, Massachusetts, USA
  4. 4 Harvard Medical School, Massachusetts General Hospital, Boston, Massachusetts, USA
  5. 5 Division of Neurocritical Care and Emergency Neurology, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts, USA
  1. Correspondence to Dr Andreas Charidimou, Harvard Medical School, J. Kistler Stroke Research Center, Massachusetts General Hospital, Boston, MA 02114, USA; andreas.charidimou.09{at}


Introduction The characteristics and natural history of acute non-vitamin K antagonists oral anticoagulants (NOAC)-associated intracerebral haemorrhage (ICH) are largely unknown. We performed a comprehensive systematic review and meta-analysis to compare baseline ICH volume, haematoma expansion and clinical outcomes between NOAC-ICH versus vitamin K antagonists-ICH (VKA-ICH).

Methods We searched PubMed and conference abstracts for observational studies comparing baseline characteristics and outcomes in patients with NOAC-ICH versus VKA-ICH using an appropriate keyword/MeSH term search strategy. Data were extracted following PRISMA and MOOSE guidelines. The main outcome measures were mortality and unfavourable functional outcome (modified Rankin Score: 4–6) at discharge and at 3 months, as well as ICH volumes and haematoma expansion rates in the two groups. Random-effects models with DerSimonian-Laird weights were used for pooled estimates calculation.

Results Twelve studies including 393 NOAC-ICH and 3482 VKA-ICH were pooled in meta-analysis. There was no difference in mean ICH-volume between the two groups (standard mean difference: −0.24; 95% CI −0.52 to 0.04, p=0.093). The rates of haematoma expansion were comparable in NOAC-ICH versus VKA-ICH (OR: 0.76; 95% CI 0.49 to 1.19, p=0.236). We did not find any difference between patients with NOAC-ICH versus VKA-ICH in all-cause mortality at discharge (OR: 0.66; 95% CI 0.42 to 1.05, p=0.077) and unfavourable functional outcome at discharge (OR: 0.77; 95% CI 0.41 to 1.44, p=0.413). The 3-month outcome was also comparable between the two ICH groups. Moderate-to-substantial statistical heterogeneity was noted.

Conclusion Our results confirm that ICH volume, haematoma expansion, mortality and functional outcome appear to be similar for NOAC-ICH versus VKA-ICH. Large prospective cohorts and updated meta-analyses are needed to provide more precise estimates.

  • intracerebral haemorrhage
  • anticoagulation
  • hematoma expansion
  • stroke
  • acute therapy
  • outcome
  • meta-analysis

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  • Contributors Planning, design: AC, GB. Acquisition of data: AC, GB, AM, MP. Funding: JNG, MEG. Drafting: AC, GB, AM, MP. Critical revisions: AC, GB, AM, MP, MEG, JNG. Guarantors: AC, GB.

  • Funding Grégoire Boulouis was supported by a Fulbright Research Grant, a Monahan Foundation Research Grant and a Philippe Foundation Grant. JNG received research funding from NIH/NINDS 5R01NS073344, Boehringer Ingelheim, Pfizer,and Portola.

  • Competing interests None declared.

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

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