Hydroxychloroquine alone or in combination with azithromycin and corrected QT prolongation in COVID-19 patients: A systematic review

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.