A comparative analysis of the safety profile of direct oral anticoagulants using the FDA adverse event reporting...

Direct oral anticoagulants (DOACs) are being increasingly used. However, unlike warfarin, less is known regarding their long-term side effects. To better evaluate the rates of DOAC-related adverse events (AEs) on a population level, we examined AEs reported to the FDA for three commonly used DOACs and warfarin.

We evaluated the FDA Adverse Event Reporting System (FAERS) database, which compiles reported drug-related AEs from 1969 onwards. The safety profiles of the included drugs were assessed by comparing AEs per outpatient prescription and with proportional reporting ratios (PRR).

Rivaroxaban had the highest proportion of reported AEs. Most notably the rate for breakthrough venous thromboembolism (VTE) was higher than other DOACs. Dabigatran had the highest reported rates of ischemic stroke. When the DOAC data were analyzed using PRR, reported rates of VTE were again higher with rivaroxaban while dabigatran again showed slightly higher than expected rates of ischemic stroke. Apixaban did not show higher than expected rates in any category.

Our analysis found rates of reported breakthrough VTE were significantly higher with rivaroxaban, while apixaban had no higher than expected rates of any studied AEs.