Guo Guimu, Song Ying, Chang Sijie, Zhang Jinhua
Department of Pharmacy, Fujian Maternity and Child Health Hospital College of Clinical Medicine for Obstetrics & Gynecology and Pediatrics, Fujian Medical University, Fuzhou, China.
Department of Pharmacy, Children's Hospital of Fudan University (Xiamen Branch), Xiamen Children's Hospital, Xiamen, China.
Naunyn Schmiedebergs Arch Pharmacol. 2025 Aug 13. doi: 10.1007/s00210-025-04501-4.
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.
新型口服抗凝药（NOACs）在临床实践中被广泛应用；然而，其相关的非出血性不良反应尚未得到充分重视。本研究基于美国食品药品监督管理局不良事件报告系统（FAERS）数据库，从真实世界的角度分析与NOACs相关的不良事件，特别关注非出血性不良反应信号，以评估NOACs安全性的差异，并为临床实践提供早期预警。本研究获取了FAERS数据库2014年7月1日至2024年3月31日的原始数据。对数据进行了去重和合并。采用报告比值比（ROR）和贝叶斯置信传播神经网络（BCPNN）方法检测NOACs与不良事件（AEs）之间的潜在信号。本研究揭示了几个新的严重不良反应信号，表明在使用NOACs时，非出血性不良反应应受到更多关注。具体而言，在三个器官系统中观察到显著的不良反应信号：先天性、家族性和遗传性疾病；妊娠、产褥期和围产期情况；以及血液和淋巴系统疾病。此外，NOACs之间存在安全性差异，每种NOAC都有其独特的不良事件。例如，达比加群与包括绞窄性腹股沟疝嵌顿、黄斑纤维化、钾失衡、酸中毒和精神状态改变等不良反应相关。对于阿哌沙班，由于潜在的不良反应包括视力损害、良性前列腺增生、甲状腺疾病和睡眠障碍，需要谨慎使用。关于依度沙班，从业者应警惕潜在的不良反应，如淋巴系统疾病、排尿困难、复视、麻疹样皮疹和谵妄。此外，利伐沙班可能导致血小板增多症、脱发、前列腺静脉曲张、月经不调、肾上腺肿大和器质性脑综合征等并发症。本研究发现，与NOACs相关的非出血性不良事件与多个器官系统有关，这在临床实践中需要高度警惕，尤其是对于一些容易被忽视的系统，如生殖系统和乳腺疾病、内分泌疾病以及精神疾病。本研究为与NOACs相关的不良反应提供了重要见解，突出了其安全性概况的多样性。
