Meta-Analysis

. 2019 Dec;266(12):3126-3135.

doi: 10.1007/s00415-019-09536-1. Epub 2019 Sep 20.

Meta-analysis of haematoma volume, haematoma expansion and mortality in intracerebral haemorrhage associated with oral anticoagulant use

David J Seiffge^{1

2

3}, Martina B Goeldlin^{4

5}, Turgut Tatlisumak^{6

7}, Philippe Lyrer⁸, Urs Fischer⁴, Stefan T Engelter^{8

9}, David J Werring¹⁰

Affiliations

¹ Stroke Research Centre, Institute of Neurology, University College London, Russell Square House, 10 Russell Square, London, UK. david.seiffge@insel.ch.
² Stroke Center and Neurology, Department of Clinical Research, University Hospital and University, Basel, Switzerland. david.seiffge@insel.ch.
³ Department of Neurology, Inselspital, Bern University Hospital, University of Bern, Bern, Switzerland. david.seiffge@insel.ch.
⁴ Department of Neurology, Inselspital, Bern University Hospital, University of Bern, Bern, Switzerland.
⁵ University Institute for Diagnostic and Interventional Neuroradiology, Inselspital, Bern University Hospital, University of Bern, Bern, Switzerland.
⁶ Department of Clinical Neuroscience/Neurology, Institute of Neurosciences and Physiology, Sahlgrenska Academy at University of Gothenburg, Gothenburg, Sweden.
⁷ Department of Neurology, Sahlgrenska University Hospital, Gothenburg, Sweden.
⁸ Stroke Center and Neurology, Department of Clinical Research, University Hospital and University, Basel, Switzerland.
⁹ Neurorehabilitation Unit, University Center for Medicine of Aging and Rehabilitation Basel, Felix Platter Hospital, University of Basel, Basel, Switzerland.
¹⁰ Stroke Research Centre, Institute of Neurology, University College London, Russell Square House, 10 Russell Square, London, UK. d.werring@ucl.ac.uk.

PMID: 31541341
PMCID: PMC6851029
DOI: 10.1007/s00415-019-09536-1

Meta-Analysis

Meta-analysis of haematoma volume, haematoma expansion and mortality in intracerebral haemorrhage associated with oral anticoagulant use

David J Seiffge et al. J Neurol. 2019 Dec.

. 2019 Dec;266(12):3126-3135.

doi: 10.1007/s00415-019-09536-1. Epub 2019 Sep 20.

Authors

David J Seiffge^{1

2

3}, Martina B Goeldlin^{4

5}, Turgut Tatlisumak^{6

7}, Philippe Lyrer⁸, Urs Fischer⁴, Stefan T Engelter^{8

9}, David J Werring¹⁰

Affiliations

¹ Stroke Research Centre, Institute of Neurology, University College London, Russell Square House, 10 Russell Square, London, UK. david.seiffge@insel.ch.
² Stroke Center and Neurology, Department of Clinical Research, University Hospital and University, Basel, Switzerland. david.seiffge@insel.ch.
³ Department of Neurology, Inselspital, Bern University Hospital, University of Bern, Bern, Switzerland. david.seiffge@insel.ch.
⁴ Department of Neurology, Inselspital, Bern University Hospital, University of Bern, Bern, Switzerland.
⁵ University Institute for Diagnostic and Interventional Neuroradiology, Inselspital, Bern University Hospital, University of Bern, Bern, Switzerland.
⁶ Department of Clinical Neuroscience/Neurology, Institute of Neurosciences and Physiology, Sahlgrenska Academy at University of Gothenburg, Gothenburg, Sweden.
⁷ Department of Neurology, Sahlgrenska University Hospital, Gothenburg, Sweden.
⁸ Stroke Center and Neurology, Department of Clinical Research, University Hospital and University, Basel, Switzerland.
⁹ Neurorehabilitation Unit, University Center for Medicine of Aging and Rehabilitation Basel, Felix Platter Hospital, University of Basel, Basel, Switzerland.
¹⁰ Stroke Research Centre, Institute of Neurology, University College London, Russell Square House, 10 Russell Square, London, UK. d.werring@ucl.ac.uk.

PMID: 31541341
PMCID: PMC6851029
DOI: 10.1007/s00415-019-09536-1

Abstract

Objective: To obtain precise estimates of age, haematoma volume, secondary haematoma expansion (HE) and mortality for patients with intracerebral haemorrhage (ICH) taking oral anticoagulants [Vitamin K antagonists (VKA-ICH) or non-Vitamin K antagonist oral anticoagulants (NOAC-ICH)] and those not taking oral anticoagulants (non-OAC ICH) at ICH symptom onset.

Methods: We conducted a systematic review and meta-analysis of studies comparing VKA-ICH or NOAC-ICH or both with non-OAC ICH. Primary outcomes were haematoma volume (in ml), HE, and mortality (in-hospital and 3-month). We calculated odds ratios (ORs) using the Mantel-Haenszel random-effects method and corresponding 95% confidence intervals (95%CI) and determined the mean ICH volume difference.

Results: We identified 19 studies including data from 16,546 patients with VKA-ICH and 128,561 patients with non-OAC ICH. Only 2 studies reported data on 4943 patients with NOAC-ICH. Patients with VKA-ICH were significantly older than patients with non-OAC ICH (mean age difference: 5.55 years, 95%CI 4.03-7.07, p < 0.0001, I² = 92%, p < 0.001). Haematoma volume was significantly larger in VKA-ICH with a mean difference of 9.66 ml (95%CI 6.24-13.07 ml, p < 0.00001; I² = 42%, p = 0.05). HE occurred significantly more often in VKA-ICH (OR 2.96, 95%CI 1.74-4.97, p < 0.00001; I² = 65%). VKA-ICH was associated with significantly higher in-hospital mortality (VKA-ICH: 32.8% vs. non-OAC ICH: 22.4%; OR 1.83, 95%CI 1.61-2.07, p < 0.00001, I² = 20%, p = 0.27) and 3-month mortality (VKA-ICH: 47.1% vs. non-OAC ICH: 25.5%; OR 2.24, 95%CI 1.52-3.31, p < 0.00001, I² = 71%, p = 0.001). We did not find sufficient data for a meta-analysis comparing NOAC-ICH and non-OAC-ICH.

Conclusion: This meta-analysis confirms, refines and expands findings from prior studies. We provide precise estimates of key prognostic factors and outcomes for VKA-ICH, which has larger haematoma volume, increased rate of HE and higher mortality compared to non-OAC ICH. There are insufficient data on NOACs.

Keywords: Haematoma expansion; Haematoma volume; Intracerebral haemorrhage; Mortality; Oral anticoagulants.

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Conflict of interest statement

DJS: scientific advisory boards: Bayer and Pfizer. Compensation for educational efforts: Stago. MBG: no disclosures. TT: academic grants from Helsinki University Central Hospital, University of Gothenburg, Sahlgrenska University Hospital, and Sigrid Juselius Foundation for research on intracerebral hemorrhages. TT has or has had research contracts with Boehringer-Ingelheim, Bayer, Pfizer, and Portola Pharm. Advisory board membership for Boehringer-Ingelheim, Bayer, Pfizer, and Lumosa Pharm. PAL: scientific advisory boards: Bayer, Daiichi-Sankyo and Boehringer Ingelheim. Funding for travel or speaker honoraria: Bayer and Boehringer Ingelheim. Research funding: Boehringer Ingelheim. UF: consultant for Medtronic and Stryker, a Co-PI of the SWITCH trial and the ELAN trial (both supported by the Swiss National Science Foundation and the Swiss Heart Foundation) and of the SWIFT DIRECT trial (supported by Medtronic). Speaker honoraria payed to the institution by AMGEN. STE: received funding for travel or speaker honoraria from Bayer, Boehringer Ingelheim and Daiichi-Sankyo. He has served on scientific advisory boards for Bayer, Boehringer Ingelheim, BMS/Pfizer, and MindMaze and on the editorial board of Stroke. His institutions have received an educational grant from Pfizer, compensation from Stago for educational efforts and research support from Daiichi-Sankyo, the Science Funds [Wissenschaftsfonds] of the University Hospital Basel, the University Basel, the “Freiwillige Akademische Gesellschaft Basel”, the Swiss Heart Foundation, and the Swiss National Science Foundation. DJW: speaker honoraria from Bayer AG. MP reports honoraria as a member of the speaker bureau of Aspen, Sanofi-Aventis, Boehringer Ingelheim, Bayer AG, Bristol-Myers Squibb, Medtronic, and Pfizer.

Figures

**Fig. 1**
Mean difference of ICH volume in VKA-ICH compared to non-OAC ICH

**Fig. 2**
Rate of haematoma expansion (HE) in VKA-ICH compared to non-OAC ICH

**Fig. 3**
In-hospital mortality in VKA-ICH compared to non-OAC ICH

**Fig. 4**
3-month mortality in VKA-ICH compared to non-OAC ICH

See this image and copyright information in PMC

References

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Meta-analysis of haematoma volume, haematoma expansion and mortality in intracerebral haemorrhage associated with oral anticoagulant use

Affiliations

Meta-analysis of haematoma volume, haematoma expansion and mortality in intracerebral haemorrhage associated with oral anticoagulant use

Authors

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Abstract

Conflict of interest statement

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