An Umbrella Review of Clinical Efficacy and Adverse Cardiac Events Associated with Hydroxychloroquine or Chloroquine with or Without Azithromycin in Patients with COVID-19

CONTEXT: The safety and efficacy of several repurposed drugs, including hydroxychloroquine and chloroquine, with or without azithromycin, were presumed to be miraculous in treating patients with COVID-19. However, as it later transpired, these therapeutic agents seem to be associated with critical adverse cardiac events. OBJECTIVES: Given the skepticism around the advantages and disadvantages of the aforementioned treatment strategies, the present study aimed to investigate the clinical efficacy and cardiac toxicity of hydroxychloroquine or chloroquine with or without azithromycin in the setting of COVID-19 infection. METHOD: This was an umbrella review conducted on patients with COVID-19 who received hydroxychloroquine or chloroquine with or without azithromycin from January 2020 to November 2020. We systematically searched PubMed, Scopus, Cochrane, ProQuest, Web of Science, and Embase databases. RESULTS: Three studies (systematic review and meta-analysis) were analyzed to evaluate the arrhythmogenic potential of hydroxychloroquine or chloroquine with or without azithromycin in patients with COVID-19 and identify the clinical efficacy of such a combination. CONCLUSIONS: We found no benefit for patients with COVID-19 who received hydroxychloroquine or chloroquine alone or in combination with azithromycin. Moreover, it is noteworthy that these medications, particularly when considering co-administration, could result in both statistically and clinically elevated risks of notorious arrhythmias, such as TdP.