Cardiovascular Safety of Azithromycin in Patients Hospitalized with Coronavirus Disease 2019: a Pre-Specified Pooled Analysis of the COALITION I and COALITION II Randomized Clinical Trials

• Published in: The American journal of cardiology
• Main Authors: Furtado, Remo Hm, Barros E Silva, Pedro Gm, Fonseca, Henrique Ar, Serpa-Neto, Ary, Correa, Thiago D, Guimarães, Hélio P, Pereira, Adriano J, Olivato, Guilherme B, Zampieri, Fernando G, Lisboa, Thiago, Junqueira, Debora Lm, Lapa, Maura G, Monfardini, Frederico, Damiani, Lucas P, Echenique, Leandro S, Gebara, Otavio E, Hoffman Filho, Conrado R, Polanczyk, Carisi A, Rohde, Luis E, Amazonas, Roberto, Machado, Flávia R, Avezum, Alvaro, Azevedo, Luciano Cp, Veiga, Viviane C, Rosa, Regis G, Lopes, Renato D, Cavalcanti, Alexandre B, Berwanger, Otavio
• Format: Journal Article
• Language: English
• Published: United States 15.12.2023
• Subjects: COVID-19; QTc interval prolongation; hydroxychloroquine; cardiac arrhythmia; azithromycin; cardiac arrest
• ISSN: 1879-1913

The cardiovascular safety from azithromycin in the treatment of several infectious diseases has been challenged. In this pre-specified pooled analysis of two multicenter randomized clinical trials, we aimed to assess whether the use of azithromycin might lead to QTc interval prolongation or clinically relevant ventricular arrhythmias. In the COALITION I I trial, 667 patients admitted with moderate Coronavirus Disease 2019 (COVID-19) were randomized to hydroxychloroquine, hydroxychloroquine plus azithromycin or standard of care. In the COALITION II trial, 447 patients with severe COVID-19 were randomized to hydroxychloroquine alone versus hydroxychloroquine plus azithromycin. The principal endpoint for the present analysis was the composite of death, resuscitated cardiac arrest or ventricular arrhythmias. The addition of azithromycin to hydroxychloroquine did not result in any prolongation of QTc interval (425.8 ± 3.6 ms versus 427.9 ± 3.9 ms, respectively; mean difference -2.1 ms; 95% CI -12.5 to 8.4 ms; p = 0.70). The combination of azithromycin plus hydroxychloroquine, when compared with hydroxychloroquine alone, did not result in increased risk of the primary endpoint (proportion of patients with events at 15 days 17.2% versus 16.0%, respectively; HR = 1.08; 95% CI 0.78 to 1.49; p = 0.65). In conclusion, in patients hospitalized with COVID-19 already receiving standard of care management (including hydroxychloroquine) the addition of azithromycin did not result in prolongation of QTc interval or increase in cardiovascular adverse events. Because azithromycin is among the mostly prescribed antimicrobial agents, our results may inform clinical practice.