Cardiovascular Safety of Azithromycin in Patients Hospitalized With COVID-19: A Prespecified Pooled Analysis of the COALITION I and COALITION II Randomized Clinical Trials.

The cardiovascular safety from azithromycin in the treatment of several infectious diseases has been challenged. In this prespecified pooled analysis of 2 multicenter randomized clinical trials, we aimed to assess whether the use of azithromycin might lead to corrected QT (QTc) interval prolongation or clinically relevant ventricular arrhythmias. In the COALITION COVID Brazil I trial, 667 patients admitted with moderate COVID-19 were randomly allocated to hydroxychloroquine, hydroxychloroquine plus azithromycin, or standard of care. In the COALITION COVID Brazil II trial, 447 patients with severe COVID-19 were randomly allocated to hydroxychloroquine alone versus hydroxychloroquine plus azithromycin. The principal end point 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 the QTc interval (425.8 ± 3.6 ms vs 427.9 ± 3.9 ms, respectively, mean difference -2.1 ms, 95% confidence interval -12.5 to 8.4 ms, p = 0.70). The combination of azithromycin plus hydroxychloroquine compared with hydroxychloroquine alone did not result in increased risk of the primary end point (proportion of patients with events at 15 days 17.2% vs 16.0%, respectively, hazard ratio 1.08, 95% confidence interval 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 the prolongation of the QTc interval or increase in cardiovascular adverse events. Because azithromycin is among the most commonly prescribed antimicrobial agents, our results may inform clinical practice. Clinical Trial Registration: NCT04322123, NCT04321278.
Competing Interests: Declaration of competing interest Dr. Furtado reports research grants and personal fees from AstraZeneca, Bayer, Servier, and Apsen and research grants (received from his institution) from Pfizer, Libbs, Brazilian Ministry of Health, and University Health Network. Dr. Fonseca received research grants from AstraZeneca, Pfizer, Essity, Aché, Colgate, BioGen, and Brazilian Ministry of Health. Dr. Barros e Silva reports reports fees and research grants from Pfizer, Roche Diagnostics, and Bayer. Dr. Pereira reports research grants from Brazilian Ministry of Health through PROADI-SUS Program (not related to this article). Dr. Polanczyk received research grants and professional fees from AstraZeneca, Bayer, Pfizer, Novartis, Roche, Sanofi, and Brazilian Ministry of Health through PROADI Programs. Dr. Veiga received grants from Brazilian Ministry of Health through PROADI-SUS Program. Dr. Rosa received research grants from Pfizer, Merck Sharp & Dohme, and Brazilian Ministry of Health. Dr. Azevedo received professional fees from Baxter, Nestle, and Merck Sharp & Dohme not related to the present work and research grants from Brazilian Ministry of Health through PROADI-SUS Program. Dr. Avezum reports research grants from Bayer, Sanofi-Pasteur, and Population Health Research Institute. Dr. Cavalcanti reports research grants from Bayer. Dr. Lopes reports research support from Bristol-Myers Squibb, GlaxoSmithKline, Medtronic, Pfizer and consulting fees from Bayer, Boehringer-Ingelheim, Bristol-Myers Squibb, Daiichi-Sankyo, GlaxoSmithKline, Medtronic, Merck, Pfizer, and Portola. Dr. Berwanger report research grants from Bayer, Pfizer, AstraZeneca, Servier, Novartis, and Boehringer-Ingelheim. The remaining authors have no competing interest to declare.
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