Serebruany Victor L, Tomek Ales, Kim Moo Hyun, Litvinov Oleg, Marciniak Thomas A
Division of Neurology, Johns Hopkins University, Baltimore, Maryland, United States.
Division of Neurology, Charles University and Motol Hospital, Prague, Czech Republic.
TH Open. 2017 Aug 30;1(2):e101-e105. doi: 10.1055/s-0037-1606301. eCollection 2017 Jul.
The U.S. Food and Drug Administration (FDA) Adverse Event (AE) Reporting System (FAERS) is a global passive surveillance repository requiring mandatory updates by pharmaceutical manufacturers. Oral antiplatelet agents (OAAs) including aspirin (acetylsalicylic acid [ASA]) are broadly used to prevent thrombosis, at the expense of extra bleeding risks. However, the OAA filing quality and their comparative patterns in FAERS are unknown. We assessed completeness of original annual FAERS reports for OAA with special attention on ASA. We extracted AE cases co-reported with OAA including ASA, clopidogrel, prasugrel, ticagrelor, vorapaxar, or their combination. The 2015 FAERS cases were examined based on OAA distribution, suspected causative role, missing gender or age, and most common AEs after ASA. A total of 1,187,729 reports qualified the inclusion criteria. The majority ( = 1,121,989) of the reports contain no reference of OAA, while 65,730 reports contain reference of at least one OAA, including 47,900 ASA cases. Therapy with ASA was heavily (>50%) underreported when used with prasugrel or ticagrelor, but still dominant (72.8%) among OAAs, followed by clopidogrel (18.7%), prasugrel (4.1%), ticagrelor (3.6%), and anecdotal vorapaxar (0.05%). Despite current recommendations, some (0.73%) reports contain multi-OAAs. The primary role of ASA in AE reporting was seldom (<1%), followed by clopidogrel (2.9%), prasugrel (3.7%), and highest for ticagrelor (9.3%). Missing gender after OAA was not common (<10%), but age was missing in approximately 25% of reports. Bleeding was the most frequent AE associated with ASA. The quality of reporting for OAA in general and ASA in particular can be improved by stricter FDA rules, better surveillance, and enforcements. Heavy ASA underreporting during dual antiplatelet therapy and missed demographic variables challenge outcome research capacities for establishing drug interactions in FAERS.
美国食品药品监督管理局（FDA）不良事件（AE）报告系统（FAERS）是一个全球性的被动监测数据库，要求制药商进行强制性更新。包括阿司匹林（乙酰水杨酸[ASA]）在内的口服抗血小板药物（OAA）被广泛用于预防血栓形成，但会增加出血风险。然而，FAERS中OAA的申报质量及其比较模式尚不清楚。我们评估了FAERS年度原始报告中OAA的完整性，特别关注了ASA。
我们提取了与OAA共同报告的AE病例，包括ASA、氯吡格雷、普拉格雷、替格瑞洛、沃拉帕沙或它们的组合。根据OAA分布、可疑因果关系、性别或年龄缺失情况以及ASA后的最常见AE对2015年FAERS病例进行了检查。
共有1,187,729份报告符合纳入标准。大多数（=1,121,989）报告未提及OAA，而65,730份报告提及了至少一种OAA，包括47,900例ASA病例。与普拉格雷或替格瑞洛联用时，ASA治疗的报告严重不足（>50%），但在OAA中仍占主导地位（72.8%），其次是氯吡格雷（18.7%）、普拉格雷（4.1%）、替格瑞洛（3.6%）和少量的沃拉帕沙（0.05%）。尽管有当前的建议，但仍有一些（0.73%）报告包含多种OAA。ASA在AE报告中的主要作用很少（<1%），其次是氯吡格雷（2.9%）、普拉格雷（3.7%），替格瑞洛最高（9.3%）。OAA后性别缺失情况不常见（<10%），但约25%的报告年龄缺失。出血是与ASA相关的最常见AE。
通过更严格的FDA规则、更好的监测和执法，可以提高OAA总体尤其是ASA的报告质量。双重抗血小板治疗期间ASA报告严重不足以及人口统计学变量缺失对在FAERS中建立药物相互作用的结果研究能力构成挑战。
