Serious bradycardia and remdesivir for coronavirus 2019 (COVID-19): a new safety concerns
Anthony Touafchia, Haleh Bagheri, Didier Carrié, Geneviève Durrieu, Agnès Sommet, Laurent Chouchana, François Montastruc
Clinical Microbiology and Infection, doi:10.1016/j.cmi.2021.02.013
Objectives: In recent clinical trials some cardiac arrhythmias were reported with use of remdesivir for COVID-19. To address this safety concern, we investigated whether use of remdesivir for COVID-19 is associated with an increased risk of bradycardia. Methods: Using VigiBase®, the World Health Organization Global Individual Case Safety Reports database, we compared the cases of bradycardia reported in COVID-19 patients exposed to remdesivir with those reported in COVID-19 patients exposed to hydroxychloroquine, lopinavir/ritonavir, tocilizumab or glucocorticoids. All reports of patients with COVID-19 registered up to the 23 September 2020 were included. We conducted disproportionality analyses allowing the estimation of reporting odds ratios (RORs) with 95% CI. Results: We found 302 cardiac effects including 94 bradycardia (31%) among the 2603 reports with remdesivir prescribed in COVID-19 patients. Most of the 94 reports were serious (75, 80%), and in 16 reports (17%) evolution was fatal. Compared with hydroxychloroquine, lopinavir/ritonavir, tocilizumab or glucocorticoids, the use of remdesivir was associated with an increased risk of reporting bradycardia (ROR 1.65; 95% CI 1.23e2.22). Consistent results were observed in other sensitivity analyses. Discussion: This post-marketing study in a real-world setting suggests that the use of remdesivir is significantly associated with an increased risk of reporting bradycardia and serious bradycardia when compared with the use of with hydroxychloroquine, lopinavir/ritonavir, tocilizumab or glucocorticoids. This result is in line with the pharmacodynamic properties of remdesivir.
Author contributions All authors conceived and designed the study. F.M. and A.T. acquired the data and did the statistical analyses. All authors analysed and interpreted the data. F.M. wrote the manuscript, and all authors critically revised the manuscript. F.M. supervised the study and is the guarantor. All authors approved the final version of the manuscript and are accountable for its accuracy.
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