Signal Mining for Non-Bleeding Adverse Event in Novel Oral Anticoagulants: A Pharmacovigilance Study Based on the FAERS Database

Abstract Backgroud: This study is based on the FAERS database and analyzes adverse events associated with NOACs from a real-world perspective, particularly focusing on non-bleeding adverse events (AEs) signals. Method: This study obtained raw data from the FAERS database, ranging from the third quarter of 2014 to the first quarter of 2024. The Reporting Odds Ratio (ROR) and Bayesian Confidence Propagation Neural Network (BCPNN) methods were employed to detect potential signals between NOACs and AEs. Result: The significant adverse reaction signals were identified across three critical organ systems: Congenital, familial, and genetic disorders; Pregnancy, puerperium, and perinatal conditions; along with Blood and lymphatic system disorders. Furthermore, the analysis revealed distinct safety profiles among the different NOACs, with each exhibiting particular AE. Specifically, dabigatran was associated with adverse reactions including Potassium imbalance, Acidosis (n=21, ROR₀₂₅=2.28, IC₀₂₅=4.60), and Mental status changes (n=46, ROR₀₂₅=1.67, IC₀₂₅=5.85). For apixaban, there is a need for caution due to potential adverse reactions including Thyroid disorders (n=109, ROR₀₂₅=1.79, IC₀₂₅=6.28), Benign prostatic hyperplasia (n=57, ROR₀₂₅=2.62, IC₀₂₅=5.67), and Sleep disturbances (n=69, ROR₀₂₅=1.24, IC₀₂₅=5.87). Concerning edoxaban, practitioners should be vigilant about potential adverse effects such as Lymphatic disorder (n=3, ROR₀₂₅=11.02, IC₀₂₅=0.74), Rash morbilliform (n=69, ROR₀₂₅=1.24, IC₀₂₅=5.87), and Delirium (n=13, ROR₀₂₅=1.54, IC₀₂₅=3.81). Additionally, rivaroxaban usage may lead to complications such as Alopecia (n=959, ROR₀₂₅=1.71, IC₀₂₅=7.61), Menstrual irregularities, and Adrenomegaly (n=4, ROR₀₂₅=2.49, IC₀₂₅=1.36). Conclusion: 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.