Systematic Reviews
Copyright ©The Author(s) 2021. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Meta-Anal. Dec 28, 2021; 9(6): 557-567
Published online Dec 28, 2021. doi: 10.13105/wjma.v9.i6.557
Hydroxychloroquine alone or in combination with azithromycin and corrected QT prolongation in COVID-19 patients: A systematic review
Haleh Ashraf, Parham Ghafouri, Sina Kazemian, Abbas Soleimani, Azadeh Sadat Naseri, Shahrokh Karbalai, Ali Kazemi Saeid
Haleh Ashraf, Research Development Center, Sina Hospital, Tehran University of Medical Sciences, Tehran 11367-46911, Iran
Haleh Ashraf, Sina Kazemian, Cardiac Primary Prevention Research Center (CPPRC), Tehran Heart Center, Tehran University of Medical Sciences, Tehran 11367-46911, Iran
Parham Ghafouri, Sina Kazemian, Students' Scientific Research Center (SSRC), Tehran University of Medical Sciences, Tehran 11367-46911, Iran
Parham Ghafouri, School of medicine, Tehran University of Medical Science, Tehran 11367-46911, Iran
Abbas Soleimani, Azadeh Sadat Naseri, Shahrokh Karbalai, Ali Kazemi Saeid, Department of Cardiology, Sina Hospital, Tehran University of Medical Sciences, Tehran 11367-46911, Iran
Author contributions: Ashraf H, Ghafouri P, Kazemian S, Soleimani A, Karbalai S designed the research study; Ashraf H, Kazemian S, Soleimani A, Sadat Naseri A, and Kazemi Saeid A performed the research; Ashraf H and Ghafouri P contributed new reagents and analytic tools; Ashraf H, Soleimani A, Sadat Naseri A, Karbalai S, and Kazemi Saeid A analyzed the data and wrote the manuscript; All authors have read and approved the final manuscript.
Conflict-of-interest statement: The authors declare that they have no competing interests.
PRISMA 2009 Checklist statement: The authors have read the PRISMA 2009 Checklist statement, and the manuscript was prepared and revised according to the PRISMA 2009 Checklist statement.
Open-Access: This article is an open-access article that was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution NonCommercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: http://creativecommons.org/Licenses/by-nc/4.0/
Corresponding author: Shahrokh Karbalai, MD, Assistant Professor, Department of Cardiology, Sina Hospital, Tehran University of Medical Sciences, Hasan Abad Sq., Tehran 11367-46911, Iran. saleh6948@tums.ac.ir
Received: June 17, 2021
Peer-review started: June 17, 2021
First decision: July 30, 2021
Revised: August 1, 2021
Accepted: November 5, 2021
Article in press: November 5, 2021
Published online: December 28, 2021
Abstract
BACKGROUND

Despite the controversies about the effectiveness of the current drug regimens for coronavirus disease 2019 (COVID-19), these drugs are still the only options available. Moreover, the safety of these drugs is yet to be confirmed. A serious concern is the occurrence of various cardiac arrhythmias, particularly QT prolongation.

AIM

To summarize the incidence and estimate the risk of QT interval prolongation in patients scheduling for conventional treatment (hydroxychloroquine alone or in combination with azithromycin) for COVID-19.

METHODS

We comprehensively searched Medline, Web of Knowledge, Google Scholar, Scopus, and Cochrane Central Register of Controlled Trials databases until October 31, 2020 for all eligible studies under the considered keywords COVID-19, arrhythmia, QT interval, therapy, azithromycin, and hydroxychloroquine until. The study protocols were established in compliance with PRISMA-P guidelines (Preferred Reporting Items for Systematic Review and Meta-Analysis – Protocols), and a nine-star Newcastle-Ottawa Scale scoring system was used to assess the methodological quality of all eligible studies. Outcome measures were corrected QT (QTc) prolongation, cardiac arrhythmias, or sudden cardiac death.

RESULTS

Fifteen studies enrolling 8298 patients with targeted COVID-19 therapeutic regimes were included. The eligible studies found a significant increase in the mean QTc interval following treatment with the described medications compared to baseline QTc with weighted standard differences in means of 0.766. The pooled prevalence rate of QTc prolongation was estimated to be 9.2% (95% confidence interval: 4.5% to 18.1%).

CONCLUSION

Hydroxychloroquine ± azithromycin regimen can significantly increase the risk of developing QTc prolongation.

Keywords: Azithromycin, COVID-19, Hydroxychloroquine, QTc interval

Core Tip: Given the greater importance of coronavirus disease 2019 worldwide, there is an ongoing controversy about the potential harms of anti-viral agents in which caused uncertainties in daily clinical practice. Given the unresolved debate, during this systematic review and meta-analysis, we investigated the association of Hydroxychloroquine (alone or in combination with azithromycin) with the risk of QT interval prolongation, cardiac arrhythmias, and sudden cardiac death. Although there are some studies about the effects of these agents, there are scarce systematic reviews and meta-analyses about both QT prolongation and risk of cardiac arrhythmias which is a distinguishing point for our study.