- •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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- Cerebral microbleeds: a guide to detection and interpretation.Lancet Neurol. 2009; 8: 165-174
- Cerebral microbleeds: a review of clinical, genetic, and neuroimaging associations.Front. Neurol. 2014; 4: 205
- Histopathologic analysis of foci of signal loss on gradient-echo T2*-weighted MR images in patients with spontaneous intracerebral hemorrhage: evidence of microangiopathy-related microbleeds.AJNR Am. J. Neuroradiol. 1999; 20: 637-642
- Small chronic hemorrhages and ischemic lesions in association with spontaneous intracerebral hematomas.Stroke. 1999; 30: 1637-1642
- Clinical diagnosis of cerebral amyloid angiopathy: validation of the Boston criteria.Neurology. 2001; 56: 537-539
- Cerebral microbleeds: histopathological correlation of neuroimaging.Cerebrovasc. Dis. 2011; 32: 528-534
- Cerebral microbleeds: where are we now?.Neurology. 2014; 83: 1304-1305
- Cerebral microbleeds and recurrent stroke risk: systematic review and meta-analysis of prospective ischemic stroke and transient ischemic attack cohorts.Stroke. 2013; 44: 995-1001
- Recurrent stroke risk and cerebral microbleed burden in ischemic stroke and TIA: a meta-analysis.Neurology. 2016; 87: 1501-1510
- Cerebral microbleeds: is antithrombotic therapy safe to administer?.Stroke. 2014; 45: 2811-2817
- Antithrombotic drug use, cerebral microbleeds, and intracerebral hemorrhage: a systematic review of published and unpublished studies.Stroke. 2010; 41: 1222-1228
- Risk vs benefit of anti-thrombotic therapy in ischaemic stroke patients with cerebral microbleeds.J. Neurol. 2008; 255: 1679-1686
- Embolic stroke, atrial fibrillation, and microbleeds: is there a role for anticoagulation?.Stroke. 2016; 47: 904-907
- MRI screening for chronic anticoagulation in atrial fibrillation.Front. Neurol. 2013; 4: 137
- New cerebral microbleeds in ischemic stroke patients on warfarin treatment: two-year follow-up.Clin. Neurol. Neurosurg. 2013;
- Prevention of stroke in patients with silent cerebrovascular disease: a scientific statement for healthcare professionals from the American Heart Association/American Stroke Association.Stroke. 2017; 48: e44-e71
- A call for researchers to join the META-MICROBLEEDS Consortium.Lancet Neurol. 2016; 15: 900
- Meta-analysis of observational studies in epidemiology: a proposal for reporting. Meta-analysis of observational studies in epidemiology (MOOSE) group.JAMA. 2000; 283: 2008-2012
- Preferred reporting items for systematic reviews and meta-analyses: the PRISMA statement.BMJ. 2009; 339b 2535
- ROBINS-I: a tool for assessing risk of bias in non-randomised studies of interventions.BMJ. 2016; 355: i4919
- Meta-analysis in clinical trials.Control. Clin. Trials. 1986; 7: 177-188
- The frequency of cerebral microbleeds increases with CHADS(2) scores in stroke patients with non-valvular atrial fibrillation.Eur. J. Neurol. 2013; 20: 502-508
- The clinical relevance of cerebral microbleeds in patients with cerebral ischemia and atrial fibrillation.J. Neurol. 2016; 263: 238-244
- Cerebral microbleeds and white matter hyperintensities in cardioembolic stroke patients due to atrial fibrillation: single-centre longitudinal study.J. Neurol. Sci. 2016; 369: 263-267
- Quantity of cerebral Microbleeds, antiplatelet therapy, and intracerebral hemorrhage outcomes: a systematic review and meta-analysis.J. Stroke Cerebrovasc. Dis. 2015;
- Cerebral microbleeds: detection, mechanisms and clinical challenges.Future Neurol. 2011; 6: 587-611
- Patient-specific decision-making for warfarin therapy in nonvalvular atrial fibrillation: how will screening with genetics and imaging help?.Stroke. 2008; 39: 3308-3315
- Can patients be anticoagulated after intracerebral hemorrhage? A decision analysis.Stroke. 2003; 34: 1710-1716
- Quantity of cerebral microbleeds, antiplatelet therapy, and intracerebral hemorrhage outcomes: a systematic review and meta-analysis.J. Stroke Cerebrovasc. Dis. 2015; 24: 2728-2737
- Antithrombotic therapy in patients with cerebral microbleeds.Curr. Opin. Neurol. 2017; 30: 38-47
- Comparison of the efficacy and safety of new oral anticoagulants with warfarin in patients with atrial fibrillation: a meta-analysis of randomised trials.Lancet. 2014; 383: 955-962
- Apixaban in patients with atrial fibrillation.N. Engl. J. Med. 2011; 364: 806-817
- Blood-pressure targets in patients with recent lacunar stroke: the SPS3 randomised trial.Lancet. 2013; 382: 507-515
- Effects of perindopril-based lowering of blood pressure on intracerebral hemorrhage related to amyloid angiopathy: the PROGRESS trial.Stroke. 2010; 41: 394-396
- Left atrial appendage occlusion device and novel oral anticoagulants versus warfarin for stroke prevention in nonvalvular atrial fibrillation: systematic review and meta-analysis of randomized controlled trials.Circ. Arrhythm. Electrophysiol. 2015; 8: 1057-1064
- Risk of bleeding with 2 doses of dabigatran compared with warfarin in older and younger patients with atrial fibrillation: an analysis of the randomized evaluation of long-term anticoagulant therapy (RE-LY) trial.Circulation. 2011; 123: 2363-2372
- Dabigatran versus warfarin in patients with atrial fibrillation.N. Engl. J. Med. 2009; 361: 1139-1151
- Rivaroxaban versus warfarin in nonvalvular atrial fibrillation.N. Engl. J. Med. 2011; 365: 883-891
- Apixaban versus warfarin in patients with atrial fibrillation.N. Engl. J. Med. 2011; 365: 981-992
- Edoxaban versus warfarin in patients with atrial fibrillation.N. Engl. J. Med. 2013; 369: 2093-2104
- Efficacy and safety of apixaban compared with aspirin in the elderly: a subgroup analysis from the AVERROES trial.Age Ageing. 2016; 45: 77-83
- Apixaban versus Antiplatelet drugs or no antithrombotic drugs after anticoagulation-associated intraCerebral HaEmorrhage in patients with Atrial Fibrillation (APACHE-AF): study protocol for a randomised controlled trial.Trials. 2015; 16: 393
- Association of cerebral microbleeds with mortality in stroke patients having atrial fibrillation.Neurology. 2014; 83: 1308-1315
Published online: April 28, 2017
Accepted: April 25, 2017
Received in revised form: March 31, 2017
Received: February 14, 2017
© 2017 Elsevier B.V. All rights reserved.