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Review
. 2021 May 13;8(5):55.
doi: 10.3390/jcdd8050055.

Effect of Hydroxychloroquine on QTc in Patients Diagnosed with COVID-19: A Systematic Review and Meta-Analysis

Angelos Arfaras-Melainis  1 , Andreas Tzoumas  2 , Damianos G Kokkinidis  3 , Maria Salgado Guerrero  1 , Dimitrios Varrias  1 , Xiaobo Xu  1 , Luis Cerna  4 , Ricardo Avendano  3 , Cameron Kemal  5 , Leonidas Palaiodimos  1 , Robert T Faillace  1
Affiliations
Review

Effect of Hydroxychloroquine on QTc in Patients Diagnosed with COVID-19: A Systematic Review and Meta-Analysis

Angelos Arfaras-Melainis et al. J Cardiovasc Dev Dis. .

Abstract

Background: Hydroxychloroquine or chloroquine with or without the concomitant use of azithromycin have been widely used to treat patients with SARS-CoV-2 infection, based on early in vitro studies, despite their potential to prolong the QTc interval of patients.

Objective: This is a systematic review and metanalysis designed to assess the effect of hydroxychloroquine with or without the addition of azithromycin on the QTc of hospitalized patients with COVID-19.

Materials and methods: PubMed, Scopus, Cochrane and MedRxiv databases were reviewed. A random effect model meta-analysis was used, and I-square was used to assess the heterogeneity. The prespecified endpoints were ΔQTc, QTc prolongation > 500 ms and ΔQTc > 60 ms.

Results: A total of 18 studies and 7179 patients met the inclusion criteria and were included in this systematic review and meta-analysis. The use of hydroxychloroquine with or without the addition of azithromycin was associated with increased QTc when used as part of the management of patients with SARS-CoV-2 infection. The combination therapy with hydroxychloroquine plus azithromycin was also associated with statistically significant increases in QTc. Moreover, the use of hydroxychloroquine alone, azithromycin alone, or the combination of the two was associated with increased numbers of patients that developed QTc prolongation > 500 ms.

Conclusion: This systematic review and metanalysis revealed that the use of hydroxychloroquine alone or in conjunction with azithromycin was linked to an increase in the QTc interval of hospitalized patients with SARS-CoV-2 infection that received these agents.

Keywords: COVID-19; QTc; QTc prolongation; SARS-CoV-2; chloroquine; coronavirus; hydroxychloroquine; torsades de pointes.

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Conflict of interest statement

The authors have no potential conflict of interest regarding the research or publication of this manuscript.

Figures

Figure 1
Figure 1
Risk of bias assessment.
Figure 2
Figure 2
PRISMA flow diagram.
Figure 3
Figure 3
Risk of developing QTc > 500 ms in patients that received hydroxychloroquine monotherapy.
Figure 4
Figure 4
Risk of developing QTc > 500 ms in patients that received azithromycin monotherapy.
Figure 5
Figure 5
Risk of developing QTc > 500 ms in patients that received combination therapy with hydroxychloroquine and azithromycin.
Figure 6
Figure 6
Risk of developing ΔQTc > 60 ms in patients that received combination therapy with hydroxychloroquine and azithromycin vs. hydroxychloroquine monotherapy.
Figure 7
Figure 7
Risk of developing ΔQTc > 60 ms in patients that received combination therapy with hydroxychloroquine and azithromycin vs. azithromycin monotherapy.
See this image and copyright information in PMC

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