Real-world safety profile of direct oral anticoagulants (DOACs): Disproportionality analysis of major bleeding events

Abstract

Background

Direct Oral Anticoagulants (DOACs) have revolutionized the management of thrombotic conditions, providing more predictable and manageable anticoagulation compared to traditional vitamin K antagonists. Despite their success, major bleeding events remain a significant concern. This study aims to assess and compare the haemorrhagic risks associated with various DOACs using data from the FDA's Adverse Event Reporting System (FAERS).

Methods

A retrospective disproportionality analysis of the FAERS database was conducted, covering the period from January 1, 2015, to December 31, 2023. The study focused on adverse bleeding events reported for DOACs. The Proportional Reporting Ratio (PRR) was calculated for each DOAC to identify disproportionate reporting of haemorrhagic events. Major haemorrhagic events were classified as those leading to hospitalization. The analysis also utilized the Medicare Part D dataset to estimate the usage of specific DOACs from 2015 to 2021.

Results

A total of 353,188 haemorrhagic events were identified, with 17,236 (4.9%) attributed to DOACs. The PRR for major haemorrhagic events was highest for Edoxaban at 14.1 (95% CI 13.93-14.85), followed by Dabigatran at 4.0 (95% CI 3.81-4.20), Apixaban at 3.53 (95% CI 3.47-3.61), and Rivaroxaban at 2.11 (95% CI 2.05-2.18). Edoxaban also had the highest PRR for cerebral haemorrhages. Medicare data indicated that Apixaban was the most commonly used DOAC (58.3%), followed by Rivaroxaban (34.5%).

Conclusions

Edoxaban shows a significantly higher risk of major and cerebral haemorrhages compared to other DOACs, while Rivaroxaban demonstrates a lower overall risk of haemorrhage. These findings emphasize the need for careful consideration of bleeding risks in DOAC therapy. Continuous post-marketing surveillance is crucial for understanding the safety profiles of DOACs in real-world clinical settings, aiding clinicians and patients in making informed decisions about anticoagulant therapy.