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

David J Seiffge; Martina B Goeldlin; Turgut Tatlisumak; Philippe Lyrer; Urs Fischer; Stefan T Engelter; David J Werring

doi:10.1007/s00415-019-09536-1

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

J Neurol. 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. [email protected].
² Stroke Center and Neurology, Department of Clinical Research, University Hospital and University, Basel, Switzerland. [email protected].
³ Department of Neurology, Inselspital, Bern University Hospital, University of Bern, Bern, Switzerland. [email protected].
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. [email protected].

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.

Publication types

Meta-Analysis
Systematic Review

MeSH terms

Anticoagulants / administration & dosage
Anticoagulants / adverse effects*
Cerebral Hemorrhage* / chemically induced
Cerebral Hemorrhage* / complications
Cerebral Hemorrhage* / mortality
Hematoma* / chemically induced
Hematoma* / etiology
Hematoma* / mortality
Hematoma* / pathology
Humans
Vitamin K / antagonists & inhibitors*

Substances

Anticoagulants
Vitamin K

Abstract

Publication types

MeSH terms

Substances

Grants and funding