Safety of the direct-acting anticoagulants in patients with atrial fibrillation: a meta-analysis

Introduction: Atrial fibrillation (AF) is known as one of the independent risk factors for stroke and might significantly increase its risk. Nowadays, direct-acting oral anticoagulants (DOACs) have been developed and demonstrated a more promising option to warfarin, the conclusion for safety is heterogeneous in different studies. It indicates the importance of comprehensive comparison of safety between DOACs and warfarin.

Material and methods: Four studies including ARISTOTLE, ENGAGE AF-TIMI 48, RE-LY and ROCKET-AF were included in the meta-analysis to perform separate meta-analyses for high-dose regimen, low-dose regimen and their combination. The events included major bleeding, intracranial haemorrhage, gastrointestinal bleeding, non-major clinically relevant and minor bleeding.

Results: Regardless of high dose or low dose regimen, DOACs were associated with lower risk of intracranial haemorrhage but due to no significant association for gastrointestinal bleeding, the overall effect measured by the major bleeding was also insignificant (High dose: RR=0.86, 95% CI 0.73 to 1.01; Low dose: RR=0.63, 95% CI 0.38 to 1.04). However, the combined result of high-dose and low-dose regimens showed DOACs were associated with lower risk of major bleeding events (RR=0.77, 95% CI 0.63 to 0.95).

Conclusions: Meta-analyses have showed the comparative safety of the direct-acting oral anticoagulants than warfarin in most endpoints and even better in intracranial haemorrhage. Therefore, without the need of INR monitoring, DOACs demonstrated promising alternatives to warfarin in prevention of stroke in patients with AF.