Written by Peter Liu
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In RCTs comparing aspirin with apixaban for ischemic stroke prevention, apixaban was associated with a nonsignificantly lower risk of intracranial hemorrhage.
Apixaban shows similar intracranial bleeding risk to aspirin in stroke prevention
In the warfarin era, anticoagulant therapy was clearly associated with an increase in bleeding risk compared to aspirin therapy, including increased risk of intracranial hemorrhage (ICH). This tradeoff – anticoagulation at the cost of severe bleeding risk – is now being challenged with direct oral anticoagulants (DOACs) such as apixaban.
A recent meta-analysis of 3 randomized control trials (n=10,626) compared the risk of ICH between apixaban vs. aspirin for stroke prevention. Two atrial fibrillation trials (AVERROES and ARTESIA) as well as one cryptogenic stroke trial (ARCADIA) were included. Apixaban was associated with a nonsignificantly lower risk of ICH (RR 0.67; 95%CI 0.43–1.08; P=0.10), a consistent trend across all 3 trials. Hemorrhagic stroke risk was also lower but nonsignificant (RR 0.72; 95% CI, 0.39–1.31; P=0.28). Results were robust across sensitivity analyses.
This meta-analysis adds to other, similar meta-analyses that support DOACs – particularly apixaban – as a medication that does not confer increased ICH risk over aspirin when used for stroke prevention. However, it is important to note that DOACs probably cause an increased risk of non-intracranial major hemorrhage, so the ICH findings do not clearly generalize outside of the head.
How does this change my practice?
Comparison of aspirin with DOAC in stroke prevention is most relevant in the area of atrial fibrillation. Due to the improved efficacy of DOACs over aspirin, with similar ICH risks, it is probably never appropriate to prescribe aspirin instead of a DOAC for stroke-risk prevention in atrial fibrillation, unless there is a separate indication for aspirin.
Source
Risk of Intracranial Hemorrhage With Apixaban Versus Aspirin Therapy: A Meta-Analysis of Randomized Controlled Trials. Stroke. 2025 Jun 4. doi: 10.1161/STROKEAHA.125.051088. Epub ahead of print. PMID: 40464082.
