Mayo Clin Proc Innov Qual Outcomes . The Cardiac Toxicity of Chloroquine or Hydroxychloroquine in COVID-19 Patients: A Systematic Review and Meta-regression Analysis

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Mayo Clin Proc Innov Qual Outcomes


. 2020 Nov 2.
doi: 10.1016/j.mayocpiqo.2020.10.005. Online ahead of print.
The Cardiac Toxicity of Chloroquine or Hydroxychloroquine in COVID-19 Patients: A Systematic Review and Meta-regression Analysis


Imad M Tleyjeh ^{1 2 3 4} , Zakariya Kashour ⁵ , Oweida AlDosary ¹ , Muhammad Riaz ⁶ , Haytham Tlayjeh ⁷ , Musa A Garbati ⁸ , Rana Tleyjeh ⁴ , Mouaz H Al-Mallah ⁹ , M Rizwan Sohail ^{2 10} , Dana Gerberi ¹¹ , Aref A Bin Abdulhak ¹² , John R Giudicessi ¹⁰ , Michael J Ackerman ¹³ , Tarek Kashour ¹⁴



Affiliations

• PMID: 33163895
• PMCID: PMC7605861
• DOI: 10.1016/j.mayocpiqo.2020.10.005

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.

Keywords: COVID-19; Chloroquine, (CQ); Chronic kidney disease, (CKD); Congestive heart failure, (CHF); Coronary artery disease, (CAD); Coronavirus disease 2019, (COVID-19); Diabetes mellitus, (DM); Hydroxychloroquine, (HCQ); Hypertension, (HTN); Intensive care unit, (ICU); QT prolongation; Severe acute respiratory syndrome coronavirus 2, (SARS-CoV-2); Torsades; Torsades de pointes, (TdP); Ventricular tachycardia, (VT); hydroxychloroquine; meta-analysis.