Clinical Pharmacology and Therapeutics (CPT) Postdoctoral Training Program, University of California San Francisco, San Francisco, CA, USA.
Skaggs School of Pharmacy and Pharmaceutical Sciences, University of California San Diego, La Jolla, CA, USA.
Sci Rep. 2020 Nov 5;10(1):19199. doi: 10.1038/s41598-020-76258-0.
Chloroquine (CQ) and hydroxychloroquine (HCQ) are on the World Health Organization's List of Essential Medications for treating non-resistant malaria, rheumatoid arthritis (RA) and systemic lupus erythematosus (SLE). In addition, both drugs are currently used off-label in hospitals worldwide and in numerous clinical trials for the treatment of SARS-CoV-2 infection. However, CQ and HCQ use has been associated with cardiac side effects, which is of concern due to the higher risk of COVID-19 complications in patients with heart related disorders, and increased mortality associated with COVID-19 cardiac complications. In this study we analyzed over thirteen million adverse event reports form the United States Food and Drug Administration Adverse Event Reporting System to confirm and quantify the association of cardiac side effects of CQ and HCQ. Additionally, we identified several confounding factors, including male sex, NSAID coadministration, advanced age, and prior diagnoses contributing to drug related cardiotoxicity. These findings may help guide therapeutic decision making and ethical trial design for COVID-19 treatment.
氯喹（CQ）和羟氯喹（HCQ）被世界卫生组织列入基本药物清单，用于治疗非耐药性疟疾、类风湿关节炎（RA）和系统性红斑狼疮（SLE）。此外，这两种药物目前在全球医院和许多临床试验中被超适应证使用，用于治疗 SARS-CoV-2 感染。然而，CQ 和 HCQ 的使用与心脏副作用相关，这令人担忧，因为心脏相关疾病患者 COVID-19 并发症的风险更高，并且 COVID-19 心脏并发症相关的死亡率也更高。在这项研究中，我们分析了来自美国食品和药物管理局不良事件报告系统的超过 1300 万份不良事件报告，以确认和量化 CQ 和 HCQ 的心脏副作用的关联性。此外，我们还确定了几个混杂因素，包括男性、非甾体抗炎药合用、高龄和既往诊断，这些因素导致了药物相关性心脏毒性。这些发现可能有助于指导 COVID-19 治疗的治疗决策和伦理试验设计。
