Research Article| Volume 378, P102-109, July 15, 2017

Intracerebral haemorrhage risk in microbleed-positive ischaemic stroke patients with atrial fibrillation: Preliminary meta-analysis of cohorts and anticoagulation decision schema

Published:April 28, 2017DOI:


      • Cerebral microbleeds raise thorny clinical questions, especially regarding future intracerebral haemorrhage risk.
      • This is a key concern in ischaemic stroke patients with AF treated with anticoagulation.
      • We present a group level meta-analysis of observational cohorts from around 1000 stroke patients.
      • We provide Class III evidence that in ischemic stroke patients with AF treated with warfarin cerebral microbleeds confer a 4-fold risk of future ICH.
      • We propose a simple data-driven anticoagulation schema.



      Whether ischaemic stroke patients with atrial fibrillation (AF) and cerebral microbleeds (CMBs) on MRI can be safely anticoagulated is a hotly debated topic. We performed a systematic review and meta-analysis of published aggregate data, to investigate the risk of subsequent intracerebral haemorrhage (ICH) based on CMBs presence in this stroke population, generally considered for oral anticoagulation. We also suggest a decision-making schema for anticoagulation use in this setting.


      We searched PubMed for relevant observational studies. Random effects models with DerSimonian-Laird weights were used to investigated the association between CMBs presence at baseline MRI and ICH or ischaemic stroke during follow-up.


      Four studies, with slightly heterogeneous design, including 990 ischaemic stroke patients were pooled in a meta-analysis (crude CMBs prevalence: 25%; 95%CI: 17%–33%). The median follow-up ranged between 17 and 37 months. The future symptomatic ICH rate was 1.6% (16/990), while recurrent ischaemic stroke rate was 5.9% (58/990). Baseline CMB presence was associated with increased risk of symptomatic ICH during follow-up compared to patients without CMBs (OR: 4.16; 95%CI: 1.54–11.25; p = 0.005). There was no association between CMBs presence and recurrent ischaemic stroke risk.


      We have shown that the presence of CMBs in cohorts of ischaemic stroke patients, most with AF on warfarin, is associated with a 4-fold increase in subsequent ICH (but not ischaemic stroke) risk (Class III evidence). These pooled estimates are useful for future trials design. We propose a simple data-driven anticoagulation schema which awaits validation and refinement as new prospective data are accumulated.


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