The Cardiac Toxicity of Chloroquine or Hydroxychloroquine in COVID-19 Patients: A Systematic Review and Meta-regression Analysis

Abstract

Objective: To systematically review the literature and estimate the risk of Chloroquine (CQ) and hydroxychloroquine (HCQ) cardiac toxicity in COVID-19 patients. Methods: We searched multiple data sources including PubMed/MEDLINE, Ovid Embase, Ovid EBM Reviews, Scopus, and Web of Science, and medrxiv.org from November 2019 through May 27, 2020. We included studies that enrolled COVID-19 patients treated with CQ or HCQ, with or without azithromycin and reported on cardiac toxicities. We performed a meta-analysis using the arcsine transformation of the different incidences. Results: A total of 19 studies with a total of 5652 patients were included. The pooled incidence of TdP arrhythmia or VT or cardiac arrest was 3 per 1000, 95% CI (0-21), I2=96%, 18 studies with 3725 patients. Among 13 studies of 4334 patients, the pooled incidence of discontinuation of CQ or HCQ due to prolonged QTc or arrhythmias was 5%, 95% CI (1-11), I2=98%. The pooled incidence of change in QTc from baseline of ≥ 60 ms or QTc ≥ 500 ms was 9%, 95% CI (3-17), I2=97%. Mean/median age, coronary artery disease, hypertension, diabetes, concomitant QT prolonging medications, ICU care, and severity of illness in the study populations explained between-studies heterogeneity. Conclusions: Treatment of COVID-19 patients with CQ or HCQ is associated with a significant risk of drug-induced QT prolongation and relatively higher incidence of TdP/VT/cardiac arrest. Therefore, these agents should not be used routinely in the management of COVID-19 disease. COVID-19 patients who are treated with antimalarials for other indications should be adequately monitored.