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Tytuł:
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Small vessel disease burden and intracerebral haemorrhage in patients taking oral anticoagulants.
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Autorzy:
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Seiffge DJ; Department of Neurology and Stroke Center, Inselspital Universitatsspital Bern, Bern, BE, Switzerland.; Stroke Research Centre, UCL Queen Square Institute of Neurology, London, UK.; Department of Neurology and Stroke Center, University Hospital Basel, Basel, Switzerland.
Wilson D; Stroke Research Centre, UCL Queen Square Institute of Neurology, London, UK.; New Zealand Brain Research Institute, University of Otago, Christchurch, New Zealand.
Ambler G; Department of Statistical Science, University College London, London, London, UK.
Banerjee G; Stroke Research Centre, UCL Queen Square Institute of Neurology, London, UK.
Hostettler IC; Stroke Research Centre, UCL Queen Square Institute of Neurology, London, UK.
Houlden H; MRC Centre for Neuromuscular Diseases, UCL Institute of Neurology and National Hospital for Neurology and Neurosurgery, London, UK.
Shakeshaft C; Stroke Research Centre, UCL Queen Square Institute of Neurology, London, UK.
Cohen H; Haemostasis Research Unit, Department of Haematology, University College London, London, London, UK.
Yousry TA; Neuroradiological Academic Unit, Department of Brain Repair & Rehabilitation, UCL Queen Square Institute of Neurology, London, UK.
Al-Shahi Salman R; Centre for Clinical Brain Sciences, University of Edinburgh Division of Medical and Radiological Sciences, Edinburgh, Edinburgh, UK.
Lip G; Liverpool Centre for Cardiovascular Science, University of Liverpool and Liverpool Heart & Chest Hospital, Liverpool, Merseyside, UK.; Aalborg Aalborg Thrombosis Research UnitThrombosis Research Unit, Department of Clinical Medicine, Aalborg University, Aalborg, Denmark.
Brown MM; Stroke Research Centre, UCL Queen Square Institute of Neurology, London, UK.
Muir K; Institute of Neuroscience & Psychology, University of Glasgow and Queen Elizabeth University Hospital, Glasgow, UK.
Jäger HR; Neuroradiological Academic Unit, Department of Brain Repair & Rehabilitation, UCL Queen Square Institute of Neurology, London, UK.
Werring DJ; Stroke Research Centre, UCL Queen Square Institute of Neurology, London, UK .
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Źródło:
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Journal of neurology, neurosurgery, and psychiatry [J Neurol Neurosurg Psychiatry] 2021 Mar 19. Date of Electronic Publication: 2021 Mar 19.
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Publication Model:
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Ahead of Print
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Typ publikacji:
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Journal Article
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Język:
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English
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Imprint Name(s):
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Publication: London : BMJ Publishing Group
Original Publication: London : British Medical Association
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References:
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Grant Information:
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G1002605 United Kingdom MRC_ Medical Research Council; MR/M009106/1 United Kingdom MRC_ Medical Research Council
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Molecular Sequence:
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ClinicalTrials.gov NCT02513316
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Entry Date(s):
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Date Created: 20210320 Latest Revision: 20240222
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Update Code:
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20240223
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PubMed Central ID:
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PMC8292570
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DOI:
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10.1136/jnnp-2020-325299
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PMID:
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33741739
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Objective: We investigated the contribution of small vessel disease (SVD) to anticoagulant-associated intracerebral haemorrhage (ICH).
Methods: Clinical Relevance of Microbleeds in Stroke-2 comprised two independent multicentre observation studies: first, a cross-sectional study of patients with ICH; and second, a prospective study of patients taking anticoagulants for atrial fibrillation (AF) after cerebral ischaemia. In patients with ICH, we compared SVD markers on CT and MRI according to prior anticoagulant therapy. In patients with AF and cerebral ischaemia treated with anticoagulants, we compared the rates of ICH and ischaemic stroke according to SVD burden score during 2 years follow-up.
Results: We included 1030 patients with ICH (421 on anticoagulants), and 1447 patients with AF and cerebral ischaemia. Medium-to-high severity SVD was more prevalent in patients with anticoagulant-associated ICH (CT 56.1%, MRI 78.7%) than in those without prior anticoagulant therapy (CT 43.5%, p<0.001; MRI 64.5%, p=0.072). Leukoaraiosis and atrophy were more frequent and severe in ICH associated with prior anticoagulation. In the cerebral ischaemia cohort (779 with SVD), during 3366 patient-years of follow-up the rate of ICH was 0.56%/year (IQR 0.27-1.03) in patients with SVD, and 0.06%/year (IQR 0.00-0.35) in those without (p=0.001); ICH was independently associated with severity of SVD (HR 5.0, 95% CI 1.9 to 12.2,p=0.001), and was predicted by models including SVD (c-index 0.75, 95% CI 0.63 to 0.85).
Conclusions: Medium-to-high severity SVD is associated with ICH occurring on anticoagulants, and independently predicts ICH in patients with AF taking anticoagulants; its absence identifies patients at low risk of ICH. Findings from these two complementary studies suggest that SVD is a contributory factor in ICH in patients taking anticoagulants and suggest that anticoagulation alone should no longer be regarded as a sufficient 'cause' of ICH.
Trial Registration: NCT02513316.
Competing Interests: Competing interests: DJS: Scientific advisory boards: Bayer and Pfizer. Compensation for educational efforts: Stago. DJW: speaking honoraria: Bayer. DJW: personal fees from Bayer and Portola.
(© Author(s) (or their employer(s)) 2021. Re-use permitted under CC BY. Published by BMJ.)
