Singh Anand Prakash, Tousif Sultan, Umbarkar Prachi, Lal Hind
Division of Cardiovascular Disease, UAB|The University of Alabama at Birmingham, Birmingham, AL 35294-1913, USA.
J Clin Med. 2020 Jun 15;9(6):1867. doi: 10.3390/jcm9061867.
In light of the favorable outcomes of few small, non-randomized clinical studies, the Food and Drug Administration (FDA) has issued an Emergency Use Authorization (EUA) to Hydroxychloroquine (HCQ) for hospitalized coronavirus disease 2019 (COVID-19) patients. In fact, subsequent clinical studies with COVID-19 and HCQ have reported limited efficacy and poor clinical benefits. Unfortunately, a robust clinical trial for its effectiveness is not feasible at this emergency. Additionally, HCQ was suspected of causing cardiovascular adverse reactions (CV-AEs), but it has never been directly investigated. The objective of this pharmacovigilance analysis was to determine and characterize HCQ-associated cardiovascular adverse events (CV-AEs). We performed a disproportionality analysis of HCQ-associated CV-AEs using the FDA adverse event reporting system (FAERS) database. The FAERS database, comprising more than 11,901,836 datasets and 10,668,655 patient records with drug-adverse reactions, was analyzed. The disproportionality analysis was used to calculate the reporting odds ratios (ROR) with 95% confidence intervals (CI) to predict HCQ-associated CV-AEs. HCQ was associated with higher reporting of right ventricular hypertrophy (ROR: 6.68; 95% CI: 4.02 to 11.17), left ventricular hypertrophy (ROR: 3.81; 95% CI: 2.57 to 5.66), diastolic dysfunction (ROR: 3.54; 95% CI: 2.19 to 5.71), pericarditis (ROR: 3.09; 95% CI: 2.27 to 4.23), torsades de pointes (TdP) (ROR: 3.05; 95% CI: 2.30 to 4.10), congestive cardiomyopathy (ROR: 2.98; 95% CI: 2.01 to 4.42), ejection fraction decreased (ROR: 2.41; 95% CI: 1.80 to 3.22), right ventricular failure (ROR: 2.40; 95% CI: 1.64 to 3.50), atrioventricular block complete (ROR: 2.30; 95% CI: 1.55 to 3.41) and QT prolongation (ROR: 2.09; 95% CI: 1.74 to 2.52). QT prolongation and TdP are most relevant to the COVID-19 treatment regimen of high doses for a comparatively short period and represent the most common HCQ-associated AEs. The patients receiving HCQ are at higher risk of various cardiac AEs, including QT prolongation and TdP. These findings highlight the urgent need for prospective, randomized, controlled studies to assess the risk/benefit ratio of HCQ in the COVID-19 setting before its widespread adoption as therapy.
鉴于少数小型非随机临床研究取得了良好结果，美国食品药品监督管理局（FDA）已发布紧急使用授权（EUA），批准羟氯喹（HCQ）用于住院的2019冠状病毒病（COVID - 19）患者。事实上，随后针对COVID - 19和HCQ的临床研究报告显示其疗效有限且临床益处不佳。不幸的是，在这种紧急情况下，针对其有效性进行大规模临床试验并不可行。此外，HCQ被怀疑会引起心血管不良反应（CV - AE），但从未进行过直接调查。本药物警戒分析的目的是确定并描述与HCQ相关的心血管不良事件（CV - AE）。我们使用FDA不良事件报告系统（FAERS）数据库对与HCQ相关的CV - AE进行了不成比例分析。对FAERS数据库进行了分析，该数据库包含超过11901836个数据集和10668655条有药物不良反应的患者记录。不成比例分析用于计算报告比值比（ROR）及95%置信区间（CI），以预测与HCQ相关的CV - AE。HCQ与右心室肥厚（ROR：6.68；95%CI：4.02至11.17）、左心室肥厚（ROR：3.81；95%CI：2.57至5.66）、舒张功能障碍（ROR：3.54；95%CI：2.19至5.71）、心包炎（ROR：3.09；95%CI：2.27至4.23）、尖端扭转型室速（TdP）（ROR：3.05；95%CI：2.30至4.10）、充血性心肌病（ROR：2.98；95%CI：2.01至4.42）、射血分数降低（ROR：2.41；95%CI：1.80至3.22）、右心室衰竭（ROR：2.40；95%CI：1.64至3.50）、完全性房室传导阻滞（ROR：2.30；95%CI：1.55至3.41）和QT间期延长（ROR：2.09；95%CI：1.74至2.52）的报告率较高有关。QT间期延长和TdP与相对较短时间内高剂量的COVID - 19治疗方案最为相关，并且是最常见的与HCQ相关的不良事件。接受HCQ治疗的患者发生各种心脏不良事件的风险较高，包括QT间期延长和TdP。这些发现凸显了迫切需要进行前瞻性、随机、对照研究，以在HCQ被广泛用作COVID - 19治疗药物之前评估其风险/获益比。
