Cardiovascular adverse events associated with hydroxychloroquine and chloroquine: A comprehensive pharmacovigilance analysis of pre-COVID-19 reports
Cardiovascular adverse events associated with hydroxychloroquine and chloroquine: A comprehensive pharmacovigilance analysis of pre-COVID-19 reports
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DOI：
10.1111/bcp.14546
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发表时间：
2020-09-22
影响因子：
3.4
通讯作者：
Maor, Elad
中科院分区：
文献类型：
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作者：
Goldman, Adam;Bomze, David;Maor, Elad
目的探讨羟氯喹（HCQ）和氯喹（CQ）在新型冠状病毒（COVID-19）大流行期间的安全性数据。我们使用美国食品和药物管理局不良事件报告系统（FAERS）数据库分析了现实世界的数据，以评估covid -19前报告中的HCQ/ cq相关心血管不良事件（CVAEs）。方法采用报告优势比（ROR）和信息成分95%可信区间下限（IC025）对FAERS数据库（2014年7月- 2019年9月）中HCQ/CQ进行歧化分析。结果全数据库包含6 677 225例报告，平均（+/- SD）年龄为53（+/- 17）岁，女性占74%。我们确定了4895例HCQ/CQ相关不良事件报告，其中696例（14.2%）为CVAEs。与全数据库相比，HCQ/CQ的使用与主要cvae报告率较高相关，包括心肌病（n = 86 [1.8%], ROR = 29.0[23.3-35.9]）、QT延长（n = 43 [0.9%], ROR = 4.5[3.3-6.1]）、心律失常（n = 117 [2.4%], ROR = 2.2[1.8-2.7]）和心力衰竭（n = 136 [2.8%], ROR = 2.2[1.9-2.7]，所有ic2bb0）。在性别和年龄组之间没有统计学上的显著差异。CVAEs常见于系统性红斑狼疮和干燥综合征患者。HCQ/ cq相关CVAEs随后的住院率和死亡率分别为39%和8%。过量报告显示QT间期延长和室性心律失常的频率增加（分别为35%和25%）。在现实环境中，HCQ/CQ治疗与各种cvae的较高报告率相关，特别是心肌病、QT间期延长、心律失常和心力衰竭。HCQ/ cq相关CVAEs导致严重后果的发生率很高，应仔细考虑作为标签外适应症，特别是对于心脏疾病患者。
Aim There is a clinical need for safety data regarding hydroxychloroquine (HCQ) and chloroquine (CQ) during the coronavirus (COVID-19) pandemic. We analysed real-world data using the U.S. Food and Drug Administration Adverse Events Reporting System (FAERS) database to assess HCQ/CQ-associated cardiovascular adverse events (CVAEs) in pre-COVID-19 reports. Methods We conducted disproportionality analysis of HCQ/CQ in the FAERS database (07/2014-9/2019), using reporting odds ratio (ROR) and the lower bound of the information component 95% credibility interval (IC025). Results The full database contained 6 677 225 reports with a mean (+/- SD) age of 53 (+/- 17) years and 74% females. We identified 4895 reports of HCQ/CQ related adverse events, of which 696 (14.2%) were CVAEs. Compared with the full database, HCQ/CQ use was associated with a higher reporting rate of major CVAEs, including cardiomyopathy (n = 86 [1.8%], ROR = 29.0 [23.3-35.9]), QT prolongation (n = 43 [0.9%], ROR = 4.5 [3.3-6.1]), cardiac arrhythmias (n = 117 [2.4%], ROR = 2.2 [1.8-2.7]) and heart failure (n = 136 [2.8%], ROR = 2.2 [1.9-2.7], all IC2 > 0). No statistically significant differences were observed between sex and age groups. CVAEs were reported more often in patients with systemic lupus erythematosus and Sjogren's syndrome. HCQ/CQ-associated CVAEs demonstrated subsequent hospitalization and mortality rates of 39% and 8%, respectively. Overdose reports demonstrated an increased frequency of QT prolongation and ventricular arrhythmias (35% and 25%, respectively). Conclusion In a real-world setting, HCQ/CQ treatment is associated with higher reporting rates of various CVAEs, particularly cardiomyopathy, QT prolongation, cardiac arrhythmias and heart failure. HCQ/CQ-associated CVAEs result in high rates of severe outcomes and should be carefully considered as an off-label indication, especially for patients with cardiac disorders.