Brain microbleeds, anticoagulation, and hemorrhage risk: Meta-analysis in stroke patients with AF

Andreas Charidimou; Christopher Karayiannis; Tae-Jin Song; Dilek Necioglu Orken; Vincent Thijs; Robin Lemmens; Jinkwon Kim; Su Mei Goh; Thanh G Phan; Cathy Soufan; Ronil V Chandra; Lee-Anne Slater; Shamir Haji; Vincent Mok; Solveig Horstmann; Kam Tat Leung; Yuichiro Kawamura; Nobuyuki Sato; Naoyuki Hasebe; Tsukasa Saito; Lawrence K S Wong; Yannie Soo; Roland Veltkamp; Kelly D Flemming; Toshio Imaizumi; Velandai Srikanth; Ji Hoe Heo; International META-MICROBLEEDS Initiative

doi:10.1212/WNL.0000000000004704

Brain microbleeds, anticoagulation, and hemorrhage risk: Meta-analysis in stroke patients with AF

Neurology. 2017 Dec 5;89(23):2317-2326. doi: 10.1212/WNL.0000000000004704. Epub 2017 Nov 8.

Authors

Andreas Charidimou¹, Christopher Karayiannis², Tae-Jin Song², Dilek Necioglu Orken², Vincent Thijs², Robin Lemmens², Jinkwon Kim², Su Mei Goh², Thanh G Phan², Cathy Soufan², Ronil V Chandra², Lee-Anne Slater², Shamir Haji², Vincent Mok², Solveig Horstmann², Kam Tat Leung², Yuichiro Kawamura², Nobuyuki Sato², Naoyuki Hasebe², Tsukasa Saito², Lawrence K S Wong², Yannie Soo², Roland Veltkamp², Kelly D Flemming², Toshio Imaizumi², Velandai Srikanth², Ji Hoe Heo²; International META-MICROBLEEDS Initiative

Affiliations

¹ From the J. Philip Kistler Stroke Research Center (A.C.), Department of Neurology, Massachusetts General Hospital; Harvard Medical School (A.C.), Boston, MA; META-MICROBLEEDS Initiative/Consortium (A.C.); Stroke and Ageing Research Centre (C.K., S.M.G., T.G.P., R.V.C., V.S.), Department of Medicine, School for Clinical Sciences at Monash Health, Monash University, Melbourne, Australia; Department of Neurology (J.H.H.), Yonsei University College of Medicine, Seoul, Korea; Sisli Hamidiye Etfal Education and Research Hospital (D.N.O.), Department of Neurology, Istanbul, Turkey; Department of Neurology (V.T.), Austin Health and Florey Institute of Neuroscience and Mental Health, Heidelberg, Victoria, Australia; Department of Neurology (J.K.), CHA Bundang Medical Centre, CHA University, Seongnam, Korea; Stroke Unit (T.G.P., V.S.), Neurosciences, and Neuroradiology Service (C.S., R.V.C., L.-A.S.), Monash Imaging, Monash Health, Melbourne, Australia; Department of Neurology (S.H.), Mayo Clinic, Rochester, MN; Department of Medicine and Therapeutics (V.M., K.T.L., L.K.S.W., Y.S.), Chinese University of Hong Kong; Department of Neurology (S.H., R.V., T.I.), University of Heidelberg, Germany; Department of Internal Medicine (Y.K., N.S., N.H., T.S.), Cardiovascular, Respiratory and Neurology Division, Asahikawa Medical University, Japan; Department of Stroke Medicine (R.V.), Division of Brain Sciences, Imperial College London, UK; Department of Neurosurgery (K.D.F.), Kushiro City General Hospital, Hokkaido, Japan; KU Leuven-University of Leuven (R.L.), Department of Neurosciences, Experimental Neurology and Leuven Research Institute for Neuroscience and Disease; VIB (R.L.), Vesalius Research Center, Laboratory of Neurobiology; University Hospitals Leuven (R.L.), Department of Neurology, Belgium; and Department of Neurology (T.-J.S.), College of Medicine, Ewha Woman's University, Yangcheon-gu, Seoul, Korea. andreas.charidimou.09@ucl.ac.uk.
² From the J. Philip Kistler Stroke Research Center (A.C.), Department of Neurology, Massachusetts General Hospital; Harvard Medical School (A.C.), Boston, MA; META-MICROBLEEDS Initiative/Consortium (A.C.); Stroke and Ageing Research Centre (C.K., S.M.G., T.G.P., R.V.C., V.S.), Department of Medicine, School for Clinical Sciences at Monash Health, Monash University, Melbourne, Australia; Department of Neurology (J.H.H.), Yonsei University College of Medicine, Seoul, Korea; Sisli Hamidiye Etfal Education and Research Hospital (D.N.O.), Department of Neurology, Istanbul, Turkey; Department of Neurology (V.T.), Austin Health and Florey Institute of Neuroscience and Mental Health, Heidelberg, Victoria, Australia; Department of Neurology (J.K.), CHA Bundang Medical Centre, CHA University, Seongnam, Korea; Stroke Unit (T.G.P., V.S.), Neurosciences, and Neuroradiology Service (C.S., R.V.C., L.-A.S.), Monash Imaging, Monash Health, Melbourne, Australia; Department of Neurology (S.H.), Mayo Clinic, Rochester, MN; Department of Medicine and Therapeutics (V.M., K.T.L., L.K.S.W., Y.S.), Chinese University of Hong Kong; Department of Neurology (S.H., R.V., T.I.), University of Heidelberg, Germany; Department of Internal Medicine (Y.K., N.S., N.H., T.S.), Cardiovascular, Respiratory and Neurology Division, Asahikawa Medical University, Japan; Department of Stroke Medicine (R.V.), Division of Brain Sciences, Imperial College London, UK; Department of Neurosurgery (K.D.F.), Kushiro City General Hospital, Hokkaido, Japan; KU Leuven-University of Leuven (R.L.), Department of Neurosciences, Experimental Neurology and Leuven Research Institute for Neuroscience and Disease; VIB (R.L.), Vesalius Research Center, Laboratory of Neurobiology; University Hospitals Leuven (R.L.), Department of Neurology, Belgium; and Department of Neurology (T.-J.S.), College of Medicine, Ewha Woman's University, Yangcheon-gu, Seoul, Korea.

PMID: 29117953
DOI: 10.1212/WNL.0000000000004704

Abstract

Objectives: To assess the association between cerebral microbleeds (CMBs) and future spontaneous intracerebral hemorrhage (ICH) risk in ischemic stroke patients with nonvalvular atrial fibrillation (AF) taking oral anticoagulants.

Methods: This was a meta-analysis of cohort studies with >50 patients with recent ischemic stroke and documented AF, brain MRI at baseline, long-term oral anticoagulation treatment, and ≥6 months of follow-up. Authors provided summary-level data on stroke outcomes stratified by CMB status. We estimated pooled annualized ICH and ischemic stroke rates from Poisson regression. We calculated odds ratios (ORs) of ICH by CMB presence/absence, ≥5 CMBs, and CMB topography (strictly lobar, mixed, and strictly deep) using random-effects models.

Results: We established an international collaboration and pooled data from 8 centers including 1,552 patients. The crude CMB prevalence was 30% and 7% for ≥5 CMBs. Baseline CMB presence (vs no CMB) was associated with ICH during follow-up (OR 2.68, 95% confidence interval [CI] 1.19-6.01, p = 0.017). Presence of ≥5 CMB was related to higher future ICH risk (OR 5.50, 95% CI 2.07-14.66, p = 0.001). The pooled annual ICH incidence increased from 0.30% (95% CI 0.04-0.55) among CMB-negative patients to 0.81% (95% CI 0.17-1.45) in CMB-positive patients (p = 0.01) and 2.48% (95% CI 1.2-6.2) in patients with ≥5 CMBs (p = 0.001). There was no association between CMBs and recurrent ischemic stroke.

Conclusions: The presence of CMB on MRI and the dichotomized cutoff of ≥5 CMBs might identify subgroups of ischemic stroke patients with AF with high ICH risk and after further validation could help in risk stratification, in anticoagulation decisions, and in guiding randomized trials and ongoing large observational studies.

Publication types

Meta-Analysis
Review

MeSH terms

Anticoagulants / adverse effects*
Anticoagulants / therapeutic use*
Atrial Fibrillation / complications*
Atrial Fibrillation / drug therapy*
Cerebral Hemorrhage / chemically induced*
Cerebral Hemorrhage / complications*
Cerebral Hemorrhage / epidemiology
Cohort Studies
Humans
Risk Factors
Stroke / complications*
Stroke / epidemiology

Substances

Anticoagulants