Stress cardiomyopathy (Takotsubo syndrome) in patients who received adrenergic agonist drugs: A pharmacovigilance study using the Japanese Adverse Drug Event Report (JADER) database
Stress cardiomyopathy (Takotsubo syndrome) in patients who received adrenergic agonist drugs: A pharmacovigilance study using the Japanese Adverse Drug Event Report (JADER) database
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DOI：
10.1016/j.jjcc.2021.08.019
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发表时间：
2021-12-02
影响因子：
2.5
通讯作者：
Toda, Tatsushi
中科院分区：
文献类型：
--
作者：
Sato, Kenichiro;Iwata, Atsushi;Toda, Tatsushi
简介：应激性心肌病或Takotsubo综合征（TTS）是一种急性和可逆的综合征，与心理或生理应激因素密切相关。虽然循环中儿茶酚胺水平的激增被怀疑是其病理生理学之一，但拟交感神经药物治疗对TTS发展的贡献仍不确定。研究方法：我们使用日本不良药物事件报告（JADER）数据库（包含2004年4月至2019年3月记录的50 0，0 0,0多例患者病例）进行了一项关联性分析，以通过计算报告比值比（ROR）检测TTS（“应激性心肌病”）作为与肾上腺素能激动剂药物使用相关的不良事件信号。结果如下：在报告给JADER的306例TTS病例中，我们确定了58例暴露于肾上腺素能激动剂药物的TTS病例，主要是女性（52/58，89.7%）和中位年龄在70岁左右的患者。在调整了年龄和性别后，大多数静脉注射的儿茶酚胺显示TTS的报告率显著较高（较低的95% ROR > 1），包括肾上腺素、去甲肾上腺素、多巴酚丁胺、多巴胺、苯肾上腺素和麻黄碱。此外，口服米多君、透皮妥洛特罗、吸入沙丁胺醇和吸入丙卡特罗也显示TTS的ROR显著更高。我们还发现了少数患有帕金森病的TTS病例，他们服用米多君或屈昔多巴，但没有接受其他肾上腺素能激动剂。结论：当前的药物警戒研究显示，使用某些肾上腺素能药物后TTS的ROR显著更高，这与早期文献中报告的TTS相关肾上腺素能药物基本一致。还提出了服用米多君或屈昔多巴与TTS发展的潜在关联。(c)2021年日本心脏病学院。由爱思唯尔有限公司出版。保留所有权利。
Introduction: Stress cardiomyopathy, or Takotsubo syndrome (TTS), is an acute and reversible syndrome developing in strong association with psychological or physiological stressors. While a surge in the circulating catecholamine level is suspected as one of its pathophysiologies, the contribution of treatment with sympathomimetic drugs to the development of TTS remains uncertain. Methods: We conducted a disproportionality analysis using the Japanese Adverse Drug Event Report (JADER) database containing more than 50 0,0 0 0 patient cases recorded between April 2004 and March 2019, to detect TTS ('stress cardiomyopathy') as adverse event signals associated with adrenergic agonist drugs usage by calculating reporting odds ratio (ROR). Results: Among 306 TTS cases reported to JADER, we identified 58 TTS cases with exposure to adrenergic agonist drugs, predominantly of women (52/58, 89.7%) and those in the median age-decades of the 70s. After adjusting for age in decades and sex, most of the intravenous catecholamines showed significantly higher reporting (lower 95% ROR > 1) for TTS, including adrenaline, noradrenaline, dobutamine, dopamine, phenylephrine, and ephedrine. In addition, peroral midodrine, transdermal tulobuterol, inhaled salbutamol, and inhaled procaterol also showed significantly higher ROR for TTS. We also identified a small number of TTS cases with Parkinson's disease taking midodrine or droxidopa, but not receiving other adrenergic agonists. Conclusion: The current pharmacovigilance study showed significantly higher RORs for TTS following the use of some of the adrenergic drugs, being mostly consistent with the TTS-related adrenergic drugs reported in earlier literature. A potential association of taking midodrine or droxidopa with the development of TTS was also suggested. (c) 2021 Japanese College of Cardiology. Published by Elsevier Ltd. All rights reserved.