Sridharan Kannan, Sivaramakrishnan Gowri
Department of Pharmacology & Therapeutics, College of Medicine & Health Sciences, Arabian Gulf University, Manama 26671, Bahrain.
Bahrain Defence Force Royal Medical Services, Riffa 28743, Bahrain.
J Clin Med. 2025 Sep 4;14(17):6262. doi: 10.3390/jcm14176262.
While anticoagulant and antiplatelet therapies are commonly combined in clinical settings, this combination increases the risk of hemorrhage. However, comparative data on the bleeding risks of different drug combinations remain limited. This study assesses hemorrhage risk associated with various anticoagulant-antiplatelet combinations using data from the USFDA Adverse Event Reporting System (AERS). Hemorrhage-related reports were extracted from the AERS database (March 2004-June 2024). Anticoagulants analyzed included warfarin, rivaroxaban, dabigatran, apixaban, edoxaban, betrixaban, and acenocoumarol; antiplatelets included aspirin, clopidogrel, ticagrelor, cilostazol, prasugrel, and dipyridamole. Disproportionality analysis using frequentist and Bayesian approaches was conducted to detect hemorrhage signals. Out of 160,715 hemorrhage reports, rivaroxaban, warfarin, and apixaban were the most frequently reported anticoagulants, while aspirin and clopidogrel were the top antiplatelets. Apixaban had the lowest reporting odds ratio for hemorrhage. The rivaroxaban-aspirin combination showed the highest hemorrhage risk, while combinations with cilostazol were the lowest. Apixaban, alone and in combination, was associated with reduced hemorrhage and mortality risks. Combining anticoagulants with antiplatelets increases hemorrhage and mortality risk. While our findings highlight potential safety signals related to hemorrhage with antithrombotic drug combinations, they remain hypothesis-generating and should not be interpreted as causal associations. Instead, they provide an initial basis for further validation in well-designed clinical cohorts where comorbidities can be adequately accounted for.
虽然抗凝和抗血小板治疗在临床环境中通常联合使用，但这种联合增加了出血风险。然而，关于不同药物组合出血风险的比较数据仍然有限。本研究使用美国食品药品监督管理局不良事件报告系统（AERS）的数据评估了各种抗凝-抗血小板组合相关的出血风险。从AERS数据库（2004年3月至2024年6月）中提取了与出血相关的报告。分析的抗凝剂包括华法林、利伐沙班、达比加群、阿哌沙班、依度沙班、贝曲沙班和醋硝香豆素；抗血小板药物包括阿司匹林、氯吡格雷、替格瑞洛、西洛他唑、普拉格雷和双嘧达莫。采用频率学派和贝叶斯方法进行不成比例分析以检测出血信号。在160715份出血报告中，利伐沙班、华法林和阿哌沙班是报告最频繁的抗凝剂，而阿司匹林和氯吡格雷是排名靠前的抗血小板药物。阿哌沙班的出血报告比值比最低。利伐沙班-阿司匹林组合显示出最高的出血风险，而与西洛他唑的组合风险最低。阿哌沙班单独使用或联合使用均与出血和死亡风险降低相关。抗凝剂与抗血小板药物联合使用会增加出血和死亡风险。虽然我们的研究结果突出了抗血栓药物组合与出血相关的潜在安全信号，但这些结果仍只是假设性的，不应被解释为因果关联。相反，它们为在能够充分考虑合并症的精心设计的临床队列中进行进一步验证提供了初步依据。
