Anticoagulants for Stroke/TIA With AF and Microbleeds?

Study Questions:

Can stroke/transient ischemic attack (TIA) patients with atrial fibrillation and cerebral microbleeds (CMBs) on magnetic resonance imaging be safely anticoagulated?

Methods:

In this self-described opinion piece, the authors used risk ratios from a 2016 meta-analysis examining the effect of CMBs on future stroke risk in patients with previous stroke or TIA. They applied the risk ratios from this meta-analysis to 12,745 patients with previous stroke/TIA enrolled in one of five recent large atrial fibrillation randomized trials (AVERROES, RE-LY, ARISTOTLE, ROCKET-AF, and ENGAGE AF-TIMI) with a goal of describing the margin of benefit or harm of antithrombotic therapy versus no antithrombotic therapy stratified according to theoretical CMB status among the trial participants.

Results:

For patients with atrial fibrillation and previous TIA/stroke on anticoagulation with 1 CMB, 2-4 CMBs, ≥5 CMBs, strictly lobar CMBs, strictly deep CMBs, mixed lobar and deep CMBs, or any CMB, the estimated absolute risk reduction (ARR) in ischemic stroke exceeded the absolute estimated rate of hemorrhagic stroke. The margin of benefit (estimated hemorrhagic stroke rate subtracted from the estimated ARR in ischemic stroke) in patients with ≥5 CMBs ranged from 4.89% (apixaban) to 8.04% (rivaroxaban). For patients with atrial fibrillation and previous TIA/stroke on aspirin 81 mg with 1 CMB, 2-4 CMBs, ≥5 CMBs, strictly lobar CMBs, strictly deep CMBs, mixed lobar and deep CMBs, or any CMB, the absolute estimated rate of hemorrhagic stroke exceeded the ARR in ischemic stroke (-9.74% for ≥5 CMBs).

Conclusions:

For patients with atrial fibrillation and previous TIA/stroke with CMB(s), the benefit of anticoagulation in preventing ischemic stroke appears to outweigh the risk of hemorrhagic stroke. For patients with atrial fibrillation and previous TIA/stroke with CMB(s), the risk of aspirin appears to outweigh the benefits.

Perspective:

It is important to note that the authors applied risk ratios from patients without atrial fibrillation (from the 2016 meta-analysis) to patients with atrial fibrillation (in the five randomized trials), which may lead to inaccurate conclusions. This analysis does not allow for conclusions about one anticoagulant’s safety in CMB patients relative to another’s given the indirect nature of the comparisons. This study’s results may help justify a future placebo-controlled randomized trial of anticoagulation versus placebo in TIA/stroke patients with atrial fibrillation and CMBs.

Keywords: Anticoagulants, Aspirin, Atrial Fibrillation, Fibrinolytic Agents, Hemorrhage, Intracranial Hemorrhages, Ischemic Attack, Transient, Magnetic Resonance Imaging, Primary Prevention, Stroke, Vascular Diseases


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