Abstract Body (Do not enter title and authors here): BACKGROUND
While non-vitamin K antagonist oral anticoagulants (NOACs) are more effective than single antiplatelets (mostly low-dose aspirin) at reducing stroke risk in patients with atrial fibrillation (AF), differences in bleeding risk between NOACs and single-dose antiplatelets across various populations remain unclear.

AIM
We performed a systematic review and meta-analysis of randomized controlled trials (RCTs) comparing bleeding outcomes of NOACs versus single antiplatelet therapy.

METHODS
We searched MEDLINE, EMBASE, and CENTRAL to June 2024 for RCTs that compared NOAC (therapeutic doses used for stroke prevention in AF patients) versus single antiplatelet therapy for a treatment duration of ≥3 months. For the meta-analyses, we used fixed-effects models and reported results as summary risk ratios (RRs). We used Risk of Bias 2 and GRADE to assess the quality and certainty of the evidence.

RESULTS
Eight RCTs with 26,194 participants were included. Mean follow-up time was 18 (±13) months. NOACs included in the studies were apixaban (4 studies), rivaroxaban (2 studies), and dabigatran (2 studies). All studies used low-dose aspirin as the comparator. When compared to aspirin, NOACs had a higher risk of major bleeding (326/13107 [2.5%] vs. 239/13087 [1.8%] events; RR 1.36 95% CI 1.15-1.60, I²=52%, 8 trials; high certainty) (Figure A), gastrointestinal bleeding (104/8803 [1.2%] vs. 74/8788 [0.8%] events; RR 1.39; 95%CI, 1.04-1.87; I²=0%; 5 trials; high certainty), and clinically relevant non-major bleeding (318/10397 [3.1%] vs. 230/10395 [2.2%] events; RR 1.38; 95%CI, 1.17-1.63; I²=16%; 5 trials; high certainty). There was no difference in the risk of intracranial hemorrhage (88/13107 [0.7%] vs. 84/13087 [0.6%] events; RR 1.04, 95%CI 0.78-1.41; I²=48%; 9 trials; high certainty) (Figure B) nor fatal bleeding (22/12412 [0.2%] vs. 28/12392 [0.2%] events; RR 0.78; 95%CI, 0.45-1.36; I²=8%; 6 trials; high certainty).

CONCLUSION
When compared to aspirin, NOACs are associated with an increased risk of major bleeding and clinically relevant non-major bleeding, but not intracranial hemorrhage. These data are important to inform patients about the risks of antithrombotic treatment.