Signal mining for non-bleeding adverse event in novel oral anticoagulants: a pharmacovigilance study based on FAERS database

Abstract

Novel oral anticoagulants (NOACs) are extensively utilized in clinical practice; however, their associated non-bleeding adverse reactions have not been adequately emphasized. This study is based on the FDA Adverse Event Reporting System (FAERS) database and analyzes adverse events associated with NOACs from a real-world perspective, particularly focusing on non-bleeding adverse reaction signals, to assess differences in the safety of NOACs and provide early warnings for clinical practice. This study obtained raw data from the FAERS database, ranging from July 1, 2014, to March 31, 2024. The data were deduplicated and merged. The reporting odds ratio (ROR) and Bayesian confidence propagation neural network (BCPNN) methods were employed to detect potential signals between NOACs and adverse events (AEs). This study reveals several new and severe adverse reaction signals, indicating non-bleeding adverse effects should receive greater attention when using NOACs. Specifically, significant adverse reaction signals were observed in three organ systems: congenital, familial, and genetic disorders; pregnancy, puerperium, and perinatal conditions; along with blood and lymphatic system disorders. Furthermore, there are differences in safety among NOACs, and each NOAC has its own unique AEs. For example, dabigatran is associated with adverse reactions including incarcerated inguinal hernia strangulated, macular fibrosis, potassium imbalance, acidosis, and mental status changes. For apixaban, there is a need for caution due to potential adverse reactions including visual impairment, benign prostatic hyperplasia, thyroid disorders, and sleep disturbances. Concerning edoxaban, practitioners should be vigilant about potential adverse effects such as lymphatic disorder, dysuria, diplopia, rash morbilliform, and delirium. Additionally, rivaroxaban may lead to complications such as thrombocytosis, alopecia, prostatic varices, menstrual irregularities, adrenomegaly, and organic brain syndrome. This study has found that the non-bleeding adverse events associated with NOACs are linked to multiple organ systems, which requires high vigilance in clinical practice, especially for some easily overlooked systems such as the reproductive system and breast disorders, endocrine disorders, and psychiatric disorders. This research provides important insights into the adverse reactions related to NOACs, highlighting the diversity of their safety profiles.

Keywords: Adverse events; FAERS database; Non-bleeding; Novel oral anticoagulants; Pharmacovigilance.