Gozzo Lucia, Navarria Andrea, Benfatto Giuseppe, Longo Laura, Mansueto Silvana, Sottosanti Laura, Pani Luca, Salomone Salvatore, Drago Filippo
Department of Biomedical and Biotechnological Sciences, Section of Pharmacology, University of Catania, Via S. Sofia 97, Catania, Italy.
UNIFARM Research Centre, Catania, Italy.
Clin Drug Investig. 2017 Nov;37(11):1067-1081. doi: 10.1007/s40261-017-0566-4.
According to the Italian National Report on drug use, thienopyridines (ticlopidine, clopidogrel and prasugrel) and ticagrelor represent the most prescribed antiplatelet agents, beside aspirin. The aim of this study was to analyse the safety profile of these drugs using data from spontaneous reporting of suspected adverse reactions (ADRs).
Suspected ADRs for ticlopidine, clopidogrel, prasugrel and ticagrelor, reported on the Italian National Pharmacovigilance Network between January 2009 and December 2016, were included in the analysis. All suspected ADRs were classified by frequency, seriousness, outcome, age and system organ class.
Clopidogrel showed the highest absolute number of suspected ADRs, followed by ticlopidine. However, these data need to be contextualized in view of the differences in marketing authorization dates, prescription rates and a characterization of the relative seriousness of ADRs per each drug. After the correction for prescription rate, ticagrelor showed the highest reporting trend and ticlopidine the lowest. Most ADRs occurred in the elderly, in particular for ticlopidine. Bleeding represents one of the most reported events (ticlopidine 40%, clopidogrel 26%, prasugrel 42%, ticagrelor 30%) and aspirin was the most frequently associated suspected drug. The majority of ADRs had complete recovery and were non-serious, except for ticlopidine (serious ADRs 53%). Prasugrel showed the highest percentage of 'life-threatening' events and 'death'.
Based on the analysis conducted on spontaneous ADRs reporting system in Italy, the safety profile of antiplatelet drugs seems favourable. However, the overall risk-benefit ratio of these drugs needs to be reassessed taking into account the appropriateness of use in particular populations at risk, such as the elderly. Based on this information, we believe that more attention from clinicians and/or an implementation of regulatory measures could be useful for clinical practice.
根据意大利药物使用国家报告，噻吩并吡啶类药物（噻氯匹定、氯吡格雷和普拉格雷）以及替格瑞洛是除阿司匹林之外处方量最大的抗血小板药物。本研究的目的是利用疑似不良反应（ADR）自发报告的数据来分析这些药物的安全性。
纳入2009年1月至2016年12月期间在意大利国家药物警戒网络上报的噻氯匹定、氯吡格雷、普拉格雷和替格瑞洛的疑似ADR。所有疑似ADR均按发生频率、严重程度、转归、年龄和系统器官分类进行归类。
氯吡格雷的疑似ADR绝对数量最多，其次是噻氯匹定。然而，鉴于上市许可日期、处方率以及每种药物ADR相对严重程度的差异，这些数据需要结合具体情况来看。校正处方率后，替格瑞洛的报告趋势最高，噻氯匹定最低。大多数ADR发生在老年人中，尤其是噻氯匹定。出血是报告最多的事件之一（噻氯匹定40%，氯吡格雷26%，普拉格雷42%，替格瑞洛30%），阿司匹林是最常伴随的疑似药物。除噻氯匹定外（严重ADR占53%），大多数ADR完全恢复且不严重。普拉格雷的“危及生命”事件和“死亡”百分比最高。
基于对意大利ADR自发报告系统的分析，抗血小板药物的安全性似乎良好。然而，需要重新评估这些药物的总体风险效益比，要考虑到在特定风险人群（如老年人）中使用的适宜性。基于这些信息，我们认为临床医生给予更多关注和/或实施监管措施可能对临床实践有用。
