Cardiotoxicity of Azithromycin in COVID-19: An Overall Proportion Meta-Analysis

Introduction: To explore the incidence of pro-arrhythmic effects such as corrected QT interval (QTc) prolongation, arrhythmic events and myocardial injury of azithromycin as administered for the treatment of COVID-19. Material and Methods: We searched PubMed, the Cochrane Library and Web of Science databases from inception to 18 January 2021, as well as the medRχiv preprint database from 1 August 2020 to 18 January 2021, for studies exploring the cardiotoxicity effects of azithromycin, with or without concomitant use of hydroxychloroquine, in the context of COVID-19. We performed a random effects single-arm meta-analysis of studies to calculate pooled proportion estimates for pro-arrhythmic effects. Meta-regression analyses were conducted to explain between-study heterogeneity. Results: Thirty-four studies with a total of 3088 patients were included. Among 12 studies, the incidence of >60 ms QTc prolongation from baseline was 13% (95% CI 9%–18%, I² = 73%), whereas, among 28 studies, the incidence of QTc ≥ 500 ms at follow-up was 8% (95% CI 6%–11%, I² = 78%). Still, the discontinuation rate due to QTc prolongation was only 3% (95% CI 2%–5%, I² = 55%). The absolute risk of Torsade de pointes and ventricular tachycardia was 0.2% and 0.8%, respectively. Increased age, male sex, presence of hypertension or diabetes mellitus, use of QTc prolonging medication, prolonged baseline QTc interval and indicators of disease severity such as death explained between-study heterogeneity. Conclusions: Azithromycin, with or without hydroxychloroquine, leads to a significant risk for critical QTc prolongation in patients with COVID-19. Due to its cardiotoxicity effects and its unproven efficacy in Covid19, azithromycin use should be limited to cases of bacterial co-infection.