Comparison of Hemorrhagic Risk between Prasugrel and Clopidogrel: a Retrospective Study using Adverse Drug Event Reporting Databases
Comparison of Hemorrhagic Risk between Prasugrel and Clopidogrel: a Retrospective Study using Adverse Drug Event Reporting Databases
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DOI：
10.7150/ijms.43168
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发表时间：
2020-01-01
影响因子：
3.6
通讯作者：
Ohte, Nobuyuki
中科院分区：
文献类型：
--
作者：
Hagiwara, Hiromi;Fukuta, Hidekatsu;Ohte, Nobuyuki
背景：普拉格雷比氯吡格雷更有效地抑制血小板聚集，并更快地发挥治疗作用。在排除亚洲国家的西方和南美国家进行的全球III期试验中，与氯吡格雷相比，在计划经皮冠状动脉介入治疗的急性冠状动脉综合征患者中，普拉格雷减少了缺血事件，但增加了出血风险。在日本针对类似患者的III期试验中，普拉格雷与氯吡格雷的疗效与全球试验相当，但由于患者数量不足，其安全性无法得到证实。此外，由于严格的入组标准，这些试验的结果可能不适用于常规临床实践。因此，我们通过分析日本监管机构和美国食品和药物管理局（FDA）提供的上市后药物不良事件报告，比较了普拉格雷和氯吡格雷在现实环境中的出血风险。方法：我们分析了2014年至2017年日本不良事件报告（JADER）中普拉格雷（n = 518）或氯吡格雷（n = 3452）的3970份报告，以及2009年至2019年FDA不良事件报告系统（FAERS）中普拉格雷（n = 5992）或氯吡格雷（n = 85922）的91914份报告。结果：在JADER和FAERS中，普拉格雷比氯吡格雷更频繁和显著地与出血事件报告相关。在校正了已知混杂因素（包括年龄、性别和合用药物（阿司匹林、抗凝剂和质子泵抑制剂））后，与氯吡格雷相比，普拉格雷的出血风险仍然显著（JADER中总的、颅内和胃肠道出血事件的校正报告比值比[95% CI] = 2.42[1.97-2.96]、2.45[1.85-3.24]和2.27 [1.73-2.97]，FAERS中为2.21[2.09-2.34]、1.21[1.09-1.33]和1.41[1.29-1.54]）。结论：在包括日本患者在内的现实世界患者中，发现普拉格雷的出血风险高于氯吡格雷。
Background: Prasugrel inhibits platelet aggregation more potently and exerts therapeutic action faster than clopidogrel. In the global phase III trial conducted in Western and South American countries that excluded Asian countries, prasugrel reduced ischemic events but increased hemorrhagic risk compared with clopidogrel in patients with acute coronary syndrome scheduled for percutaneous coronary intervention. In the Japanese phase III trial for similar patients, the efficacy of prasugrel compared with clopidogrel was comparable to the global trial, but the safety could not be confirmed because of an insufficient number of patients. Furthermore, given the strict enrollment criteria, the results of these trials may not be applicable to routine clinical practice. Accordingly, we compared the hemorrhagic risk of prasugrel and clopidogrel in real-world settings by analyzing adverse drug event reports in post-marketing stages provided by the Japanese regulatory authorities and the U.S. Food and Drug Administration (FDA).Methods: We analyzed a total of 3,970 reports for prasugrel (n = 518) or clopidogrel (n = 3,452) between 2014 and 2017 in the Japanese Adverse Drug Event Report (JADER) and a total of 91,914 reports for either prasugrel (n = 5,992) or clopidogrel (n = 85,922) between 2009 and 2019 in the FDA Adverse Event Reporting System (FAERS).Results: In JADER and FAERS, prasugrel was more frequently and significantly associated with hemorrhagic event reports than clopidogrel. After adjustment for known confounders including age, sex, and concomitant medications (aspirin, anticoagulants, and proton pump inhibitors), the hemorrhagic risk of prasugrel compared with clopidogrel remained significant (adjusted reporting odds ratios [95% CI] for total, intracranial, and gastrointestinal hemorrhagic events = 2.42 [1.97-2.96], 2.45 [1.85-3.24], and 2.27 [1.73-2.97] in JADER, and 2.21 [2.09-2.34], 1.21 [1.09-1.33], and 1.41 [1.29-1.54] in FAERS).Conclusions: The hemorrhagic risk was found to be greater with prasugrel than clopidogrel in real-world patients, including Japanese patients.