New Oral Anticoagulants and the Risk of Intracranial Hemorrhage: Traditional and Bayesian Meta-Analysis and Mixed Treatment Comparison of Randomized Trials of New Oral Anticoagulants in Atrial Fibrillation

Study Questions:

What is the performance of novel oral anticoagulants (NOACs) in reducing risk of intracranial hemorrhage (ICH)?


This was a meta-analysis of randomized trials that compared NOACs with conventional anticoagulants, aspirin, or placebo for stroke prevention in patients with atrial fibrillation (AF). Statistical analyses were used to perform a comparison with all comparators and among themselves.


The authors identified six studies (one administering dabigatran, two administering rivaroxban, and three administering apixaban), with NOACs being compared against two comparators (warfarin and aspirin) in a population of 57,491 patients. NOACs significantly reduced the risk of ICH against all comparators (odds ratio, 0.49; 95% confidence interval, 0.36-0.65). There was no statistically significant difference among the three NOACs. Dabigatran 110 mg twice daily was associated with a rate of bleeding comparable to that of aspirin (0.45% vs. 0.46%, respectively).


In this meta-analysis, NOACs were uniformly associated with a reduced risk of ICH when used for stroke prevention in AF, when compared to conventional anticoagulants or aspirin.


The current analysis provides important insight to inform decision making about anticoagulation in patients with AF and risk for ICH. The limitations of the meta-analysis aside, these data may suggest that NOACs are acceptable and safe options in patients with AF at risk of ICH, but qualifying for thromboprophylaxis for ischemic stroke.

Clinical Topics: Anticoagulation Management

Keywords: Stroke, Intracranial Hemorrhages, Warfarin

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