OBJECTIVES: Hemorrhage or bleeding is the common manifestation with anti-coagulant therapy. Risk quantification of hemorrhagic profile is important with extensive use of Direct acting Oral Anti-coagulants (DOACs). This study aimed to quantify the risk of bleeding associated with DOACs using disproportionality analysis of US FDA Adverse Event Reporting System (FAERS).

METHODS: The analysis had been carried out by using publicly available FAERS data from October 2010 to September 2020. Disproportionality analysis was performed using Reporting Odds Ratio (ROR) and Proportional Reporting Ratio (PRR) with 95% confidence intervals (CI). The Preferred Term (PT) “Bleed”, “Bleeding”, “Hemorrhage” and “Haemorrhage” has been used to search for event of interest. OpenVigil 2.1 was used for data retrieval and analysis.

RESULTS: A total of 48,425 reports have been identified in the FDA database for PTs. Amongst which 11,166 (23.05%) reports were DOACs with Rivaroxaban (12.23%) sharing the maximun percentage followed by Apixaban (5.56%), Dabigatran (5.07%) and Edoxaban (0.17%). DOACs with the highest risk estimates were Rivaroxaban (ROR 13.19, 95% CI 12.82-13.56; PRR 12.49, 95% CI 12.16‐12.82), Dabigatran (ROR 9.9, 95% CI 9.5-10.32; PRR 9.48, 95% CI 9.11‐9.87) followed by Apixaban (ROR 6.86, 95% CI 6.60-7.14; PRR 6.67, 95% CI 6.42‐6.93). Edoxaban found to have least risk (ROR 4.31, 95% CI 3.47 -5.34; PRR 4.23, 95% CI 3.46‐5.34). The ROR and PRR were recalculated after removing the concomitant co-administered drugs with DOACs and the signal strength was found to be significant.

CONCLUSIONS: Among DOACs, Rivaroxaban has higher risk of hemorrhage followed by Dabigatran, Apixaban and Edoxaban. Healthcare professionals must be aware of these risk association amongst different DOACs which could help in reduction of such adverse events.