Serious Cardiovascular Adverse Events Associated with Hydroxychloroquine/Chloroquine Alone or with Azithromycin in Patients with COVID-19: A Pharmacovigilance Analysis of the FDA Adverse Event Reporting System (FAERS)
单位：[1]Department of Pharmacy, Beijing Friendship Hospital, Capital Medical University, Beijing, China医技科室药学部首都医科大学附属北京友谊医院[2]Department of Biostatistics, University of North Carolina at Chapel Hill Gillings School of Global Public Health, Chapel Hill, USA[3]Department of Pharmacy, Beijing Cancer Hospital, Beijing, China[4]Department of Epidemiology, Gillings School of Global Public Health, University of North Carolina at Chapel Hill, 2101 McGavran‑Greenberg Hall, Campus Box 7453, Chapel Hill 27599, USA[5]Department of Medicine, University of North Carolina at Chapel Hill School of Medicine, Chapel Hill, USA[6]Department of Pharmaceutical Outcomes and Policy, University of North Carolina School of Pharmacy, Chapel Hill, USA[7]Cecil G. Sheps Center for Health Services Research, University of North Carolina at Chapel Hill, Chapel Hill, USA[8]Peking University Clinical Research Institute, Peking University First Hospital, Beijing, China[9]Department of Epidemiology and Biostatistics, Arnold School of Public Health, University of South Carolina, Columbia, USA
Background The use of hydroxychloroquine or chloroquine (HCQ/CQ) as monotherapy or combined with azithromycin for the treatment of coronavirus disease 2019 (COVID-19) may increase the risk of serious cardiovascular adverse events (SCAEs). Objective Our objective was to describe and evaluate the risk of SCAEs with HCQ/CQ as monotherapy or combined with azithromycin compared with that for therapeutic alternatives. Methods We performed a disproportionality analysis and descriptive case series using the US FDA Adverse Event Reporting System. Results Compared with remdesivir, HCQ/CQ was associated with increased reporting of SCAEs (reporting odds ratio [ROR] 2.1; 95% confidence interval [CI] 1.8-2.5), torsade de pointes (TdP)/QTc prolongation (ROR 35.4; 95% CI 19.4-64.5), and ventricular arrhythmia (ROR 2.5; 95% CI 1.6-3.9); similar results were found in comparison with other therapeutic alternatives. Compared with lopinavir/ritonavir, HCQ/CQ was associated with increased reporting of ventricular arrhythmia (ROR 10.5; 95% CI 3.3-33.4); RORs were larger when HCQ/CQ was used in combination with azithromycin. In 2020, 312 of the 575 reports of SCAEs listed concomitant use of HCQ/CQ and azithromycin, including QTc prolongation (61.4%), ventricular arrhythmia (12.0%), atrial fibrillation (8.2%), TdP (4.9%), and cardiac arrest (4.4%); 88 (15.3%) cases resulted in hospitalization and 79 (13.7%) resulted in death. In total, 122 fatal QTc prolongation-related cardiovascular reports were associated with 1.4 times higher odds of reported death than those induced by SCAEs; 87 patients received more than one QTc-prolonging agent. Conclusions Patients treated with HCQ/CQ monotherapy or HCQ/CQ + azithromycin may be at increased risk of SCAEs, TdP/QTc prolongation, and ventricular arrhythmia. Cardiovascular risks need to be considered when evaluating the benefit/harm balance of treatment with HCQ/CQ, especially with the concurrent use of QTc-prolonging agents and cytochrome P450 3A4 inhibitors when treating COVID-19.
第一作者单位：[1]Department of Pharmacy, Beijing Friendship Hospital, Capital Medical University, Beijing, China
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推荐引用方式(GB/T 7714)：
Zhao Ying,Zhang Jingru,Zheng Kai,et al.Serious Cardiovascular Adverse Events Associated with Hydroxychloroquine/Chloroquine Alone or with Azithromycin in Patients with COVID-19: A Pharmacovigilance Analysis of the FDA Adverse Event Reporting System (FAERS)[J].DRUGS-REAL WORLD OUTCOMES.2022,9(2):231-241.doi:10.1007/s40801-022-00300-y.
APA：
Zhao, Ying,Zhang, Jingru,Zheng, Kai,Thai, Sydney,Simpson, Ross J., Jr....&Wang, Tiansheng.(2022).Serious Cardiovascular Adverse Events Associated with Hydroxychloroquine/Chloroquine Alone or with Azithromycin in Patients with COVID-19: A Pharmacovigilance Analysis of the FDA Adverse Event Reporting System (FAERS).DRUGS-REAL WORLD OUTCOMES,9,(2)
MLA：
Zhao, Ying,et al."Serious Cardiovascular Adverse Events Associated with Hydroxychloroquine/Chloroquine Alone or with Azithromycin in Patients with COVID-19: A Pharmacovigilance Analysis of the FDA Adverse Event Reporting System (FAERS)".DRUGS-REAL WORLD OUTCOMES 9..2(2022):231-241
