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

Journal article
Authors D. J. Seiffge
M. B. Goeldlin
Turgut Tatlisumak
P. Lyrer
U. Fischer
S. T. Engelter
D. J. Werring
Published in Journal of Neurology
Volume 266
Issue 12
Pages 3126-3135
ISSN 0340-5354
Publication year 2019
Published at Institute of Neuroscience and Physiology, Department of Clinical Neuroscience
Pages 3126-3135
Language en
Keywords Oral anticoagulants, Intracerebral haemorrhage, Haematoma volume, Mortality, Haematoma expansion, vitamin-k antagonists, intracranial hemorrhage, antithrombotic therapy, warfarin, reversal, pretreatment, guidelines, management, intensity, prognosis, Neurosciences & Neurology
Subject categories Neurosciences, Neurology


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, I-2 = 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; I-2 = 42%, p = 0.05). HE occurred significantly more often in VKA-ICH (OR 2.96, 95%CI 1.74-4.97, p < 0.00001; I-2 = 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, I-2 = 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, I-2 = 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.

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