key: cord-261186-4p1cwb2e
authors: Guzman-Prado, Yuli
title: Recent findings on cardiovascular safety with the use of chloroquine and hydroxychloroquine for COVID-19.
date: 2020-06-09
journal: Am J Cardiol
DOI: 10.1016/j.amjcard.2020.06.003
sha: 
doc_id: 261186
cord_uid: 4p1cwb2e

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and found no significant differences in the likelihood of abnormal electrocardiogram findings (defined as arrhythmia or prolonged QT interval) between groups, however, the researchers highlight that cardiac arrest was more likely in the group treated with HCQ plus AZ (adjusted OR 2.13; 95% CI 1.12 -4.05). No significant differences in in-hospital mortality were found. In order to elucidate if the finding of cardiac arrest was mediated or not by mechanical ventilation, the authors performed a stratified analysis and indicated that in the group of patients who did not receive mechanical ventilation, the risk for cardiac arrest remained increased for HCQ alone compared with AZ alone (adjusted OR 3.01 95% CI 1.07-8.51). The analysis performed in this study was adjusted for likely confounders, including comorbidities, demographics and disease severity. However, due to the observational study design it is possible that some amount of unmeasured confounding remains.

Later on, Mehra et al (9), reported a large international observational registry including data from 96032 patients from 671 hospitals in six continents (mainly North America and Europe) who received CQ (n=1868); CQ plus macrolide (n=3783); HCQ (n=3016); HCQ plus macrolide (n=6221) versus none of these drugs (n=81144) and found that the use of CQ or HCQ with or without macrolides was independently associated with a higher risk of in-hospital mortality and an increased frequency of de-novo ventricular arrhythmia (non-sustained or sustained ventricular tachycardia or ventricular fibrillation). The authors state that the combination of CQ or HCQ with a macrolide increased the hazard of de-novo ventricular arrhythmias: CQ with a macrolide (HR 4.01; 95% CI 3.34 -4.81); CQ alone (HR 3.56; 95% CI 2.76 -4.59); HCQ with a macrolide (HR 5.10; 95% CI 4.10 -5.98) and HCQ alone (HR 2.36; 95% CI 1.93 -2.90). Predictors of ventricular arrhythmia were also investigated and the variables found to be independently associated with higher risk of de-novo ventricular arrhythmias were CQ or HCQ with or without macrolides and baseline comorbidities such as coronary artery disease, congestive heart failure, history of cardiac arrhythmia, and chronic obstructive pulmonary disease. The researchers argue that the presence of underlying cardiovascular disease could represent a partial explanation of the cardiovascular toxicity associated with the use of CQ or HCQ particularly with the combination of macrolides. Notably, a propensity score matching analysis was conducted to mitigate potential confounders. Moreover, Cox proportional hazards models and a tipping-point analysis were performed to assess the robustness of the estimates. Clearly, this study represents a potential landmark regarding safety and efficacy of CQ and HCQ, either alone or in combination with macrolides, for the treatment of COVID-19. However, the observational retrospective design limits the study's implications.

In addition to the cardiotoxic considerations mentioned by Aggarwal, et al (1), relevant cardiovascular side effects and toxicities associated with the use of repurposing drugs for the treatment of COVID-19 have been stated by researchers of cardiovascular disease who stress the risk of QT interval prolongation, thrombocytopenia and anaemia specifically with the use of CQ and HCQ (10). In conclusion, it is not clear whether the risk of toxic effects may outweigh the benefits of potential COVID-19 treatments. A decisive answer still awaits the results of high quality large randomized controlled trials.

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