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Brain microbleeds, anticoagulation, and hemorrhage risk: Meta-analysis in stroke patients with AF
Andreas Charidimou1, Christopher Karayiannis2, Tae-Jin Song2
1From 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.
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.
Insights
Cerebral microbleeds (CMBs) on MRI increase the risk of future intracerebral hemorrhage (ICH) in ischemic stroke patients with atrial fibrillation (AF) on anticoagulants. Identifying CMBs may aid in risk stratification and treatment decisions.
Area of Science:
- Neurology
- Radiology
- Cardiology
Background:
- Ischemic stroke patients with nonvalvular atrial fibrillation (AF) on oral anticoagulants face risks of both recurrent ischemic events and intracerebral hemorrhage (ICH).
- Cerebral microbleeds (CMBs) are increasingly recognized as a marker of cerebral small vessel disease.
- The association between CMBs and future ICH risk in this specific patient population requires further elucidation.
Purpose of the Study:
- To evaluate the relationship between the presence and burden of cerebral microbleeds (CMBs) and the risk of future spontaneous intracerebral hemorrhage (ICH).
- To assess whether CMBs can help identify ischemic stroke patients with AF on oral anticoagulants who are at higher risk for ICH.
Main Methods:
- A meta-analysis of cohort studies was conducted, including patients with recent ischemic stroke and AF on long-term oral anticoagulation.
- Baseline brain MRI data on CMBs and long-term stroke outcome data were pooled from 8 international centers (1,552 patients).
- Pooled annualized rates of ICH and ischemic stroke were estimated, and odds ratios (ORs) for ICH were calculated based on CMB presence, number (≥5), and topography.
Main Results:
- The prevalence of CMBs was 30%, with 7% of patients having ≥5 CMBs.
- Baseline CMB presence was significantly associated with an increased risk of ICH (OR 2.68).
- A higher burden of CMBs (≥5) was strongly linked to elevated future ICH risk (OR 5.50), with annual ICH incidence rising from 0.30% in CMB-negative to 2.48% in ≥5 CMB patients. No association was found with recurrent ischemic stroke.
Conclusions:
- The presence and number of cerebral microbleeds (CMBs) are significant predictors of future intracerebral hemorrhage (ICH) risk in ischemic stroke patients with AF on anticoagulation.
- CMB assessment on MRI may help identify high-risk subgroups for improved risk stratification and informed anticoagulation decisions.
- Further validation is needed to integrate CMB findings into clinical practice and guide ongoing research.
