Impact of Cerebral Microbleeds in Stroke Patients with Atrial Fibrillation

Ann Neurol. 2023 Jul;94(1):61-74. doi: 10.1002/ana.26642. Epub 2023 Apr 17.


Objectives: Cerebral microbleeds are associated with the risks of ischemic stroke and intracranial hemorrhage, causing clinical dilemmas for antithrombotic treatment decisions. We aimed to evaluate the risks of intracranial hemorrhage and ischemic stroke associated with microbleeds in patients with atrial fibrillation treated with vitamin K antagonists, direct oral anticoagulants, antiplatelets, and combination therapy (i.e. concurrent oral anticoagulant and antiplatelet).

Methods: We included patients with documented atrial fibrillation from the pooled individual patient data analysis by the Microbleeds International Collaborative Network. Risks of subsequent intracranial hemorrhage and ischemic stroke were compared between patients with and without microbleeds, stratified by antithrombotic use.

Results: A total of 7,839 patients were included. The presence of microbleeds was associated with an increased relative risk of intracranial hemorrhage (adjusted hazard ratio [aHR] = 2.74, 95% confidence interval = 1.76-4.26) and ischemic stroke (aHR = 1.29, 95% confidence interval = 1.04-1.59). For the entire cohort, the absolute incidence of ischemic stroke was higher than intracranial hemorrhage regardless of microbleed burden. However, for the subgroup of patients taking combination of anticoagulant and antiplatelet therapy, the absolute risk of intracranial hemorrhage exceeded that of ischemic stroke in those with 2 to 4 microbleeds (25 vs 12 per 1,000 patient-years) and ≥ 11 microbleeds (94 vs 48 per 1,000 patient-years).

Interpretation: Patients with atrial fibrillation and high burden of microbleeds receiving combination therapy have a tendency of higher rate of intracranial hemorrhage than ischemic stroke, with potential for net harm. Further studies are needed to help optimize stroke preventive strategies in this high-risk group. ANN NEUROL 2023;94:61-74.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Anticoagulants
  • Atrial Fibrillation* / complications
  • Atrial Fibrillation* / drug therapy
  • Atrial Fibrillation* / epidemiology
  • Cerebral Hemorrhage / chemically induced
  • Cerebral Hemorrhage / complications
  • Cerebral Hemorrhage / diagnostic imaging
  • Fibrinolytic Agents / therapeutic use
  • Humans
  • Intracranial Hemorrhages / chemically induced
  • Ischemic Stroke* / complications
  • Risk Factors
  • Stroke* / complications
  • Stroke* / diagnostic imaging


  • Fibrinolytic Agents
  • Anticoagulants