Dementia-related adverse events associated with direct oral anticoagulants use: a real-world, pharmacovigilance study based on the FAERS database

Direct oral anticoagulants (DOACs) are commonly used to prevent and treat thromboembolic diseases. This study aimed to assess and compare dementia related adverse events (AEs) associated with DOACs.
AEs related to DOACs from January 2014 to June 2023 were extracted from the FDA Adverse Event Reporting System (FAERS) database. Disproportionality analysis methods, including reporting odds ratio (ROR), proportional reporting ratio, Bayesian Confidence Propagation Neural Network, and Multi-Item Gamma Poisson Shrinker, were used to evaluate the association between DOACs and dementia-related AEs.
There were 12,692,968 AEs reported in FAERS after deduplication. Among these, 165, 206, 1574, and 12 dementia-related AEs that were attributed to dabigatran, rivaroxaban, apixaban, and edoxaban, respectively. Apixaban showed the strongest association with dementia-related AEs (ROR 7.66, 95% confidence interval (CI) 7.27–8.06), while rivaroxaban had the lowest ROR (0.95, 95%CI 0.83–1.09). Women exhibited higher RORs for all DOACs, with apixaban showing the most significant correlation. Subgroup analysis indicated a significant link between apixaban and dementia, dementia Alzheimer’s type and senile dementia.
Apixaban appears most associated with dementia-related AEs among DOACs, whereas rivaroxaban poses a lower risk. Further research is needed to validate these findings through large-scale prospective studies.

直接口服抗凝药（Direct oral anticoagulants, DOACs）是临床预防与治疗血栓栓塞性疾病的常用药物。本研究旨在评估并比较各类直接口服抗凝药相关的痴呆相关不良事件（adverse events, AEs）。
本研究从美国食品药品监督管理局不良事件报告系统（FDA Adverse Event Reporting System, FAERS）中提取2014年1月至2023年6月期间收录的直接口服抗凝药相关不良事件报告。采用报告比值比（reporting odds ratio, ROR）、比例报告比值、贝叶斯置信传播神经网络以及多项目伽马泊松收缩器等不成比例性分析方法，评估直接口服抗凝药与痴呆相关不良事件之间的关联。
去重后，FAERS数据库中共收录12,692,968例不良事件报告。其中，达比加群酯、利伐沙班、阿哌沙班、依度沙班相关的痴呆相关不良事件报告分别为165例、206例、1574例及12例。阿哌沙班与痴呆相关不良事件的关联强度最高（ROR=7.66，95%置信区间（confidence interval, CI）：7.27~8.06），而利伐沙班的ROR值最低（0.95，95%CI：0.83~1.09）。女性患者使用各类直接口服抗凝药后的ROR值均更高，其中阿哌沙班的相关性最为显著。亚组分析显示，阿哌沙班与痴呆、阿尔茨海默型痴呆及老年性痴呆均存在显著关联。
在各类直接口服抗凝药中，阿哌沙班与痴呆相关不良事件的关联性最强，而利伐沙班的相关风险较低。后续仍需开展大规模前瞻性研究以验证本研究结果。