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
Processing time: 193 Days and 21.1 Hours
ARTICLE HIGHLIGHTS
Research background

Current evidence suggests that using hydroxychloroquine and azithromycin for coronavirus disease 2019 (COVID-19) increases the risk of cardiac arrhythmias. Previous studies reported that these drugs caused corrected QT (QTc) prolongation, leading to life-threatening conditions like torsades de pointes and sudden cardiac death. Although both in vivo and in vitro studies recommended the combination therapy of azithromycin and hydroxychloroquine, even as the first-line approach in preventing disease, it has also led to QTc prolongation.

Research motivation

In addition to cardiac monitoring, identifying patients, who are prone to side effects, helps to minimize the potential harms. By identifying susceptible individuals, it may be possible to use other drug protocols to maintain patient survival.

Research objectives

We summarize the findings about the prevalence and the risk of QTc prolongation in patients treated with hydroxychloroquine ± azithromycin. Also, we discuss the life-threatening conditions in patients taking these medications.

Research 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. Outcome measures were QTc prolongation, cardiac arrhythmias, or sudden cardiac death.

Research 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%CI: 4.5% to 18.1%).

Research conclusions

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

Research perspectives

According to our systematic review and meta-analysis, a significant change in QTc interval following the use of hydroxychloroquine alone or in combination with azithromycin is highly expected that may be life-threatening. However, it should be noted that these changes may not be solely due to the toxicity of drugs. Interventional studies are required to confirm this hypothesis.