Abstract
Background: New Oral AntiCoagulants (NOACs) have been available for patients with non-valvular atrial fibrillation as an alternative to vitamin K antagonists, such as warfarin, for more than 6 years. Despite the findings presented in large phase 3 clinical trials, the situation might be different in routine clinical practice. Aim: This review will summarize the safety outcomes (bleeding) seen in phase 3 clinical trials and observational studies comparing NOACs with warfarin. Methods: I have used PubMed to find studies comparing NOACs with warfarin with respect to bleeding. Results: 15 studies were included in this review. Most studies found that both dabigatran and apixaban were associated with lower risk of major bleeding compared with warfarin, while rivaroxaban was associated with the same risk as warfarin. In addition, most studies found that dabigatran and rivaroxaban were associated with higher risk of gastrointestinal bleeding compared with warfarin, while apixaban was associated with similar or lower risk. All but one study found that dabigatran, rivaroxaban and apixaban were associated with significantly lower risk of intracranial bleeding compared with warfarin. No observational studies comparing edoxaban with warfarin with respect to bleeding were found. However, data from a large phase 3 clinical trial, the ENGAGE AF-TIMI 48 trial, found that edoxaban was associated with lower overall risk of major bleeding and lower risk of intracranial bleeding compared with warfarin, but higher risk of gastrointestinal bleeding. Conclusions: Data from observational studies seem to be in line with data presented in large phase 3 clinical trials. Overall risk of major bleeding seems to be slightly lower with NOACs compared with warfarin and risk of intracranial bleeding seems to be significantly lower. Risk of gastrointestinal bleeding seems to be slightly higher for some of the NOACs. The main findings are consistent across most subgroups.