Cardiac Adverse Events and Remdesivir in Hospitalized Patients With COVID-19: A Post Hoc Safety Analysis of the Randomized DisCoVeRy Trial
Vida Terzić, Joe Miantezila Basilua, Nicolas Billard, Lucie de Gastines, Drifa Belhadi, Claire Fougerou‐Leurent, Nathan Peiffer‐Smadja, Noémie Mercier, Christelle Delmas, Assia Ferrane, Aline Dechanet, Julien Poissy, Hélène Espérou, Florence Ader, Maya Hites, Claire Andréjak, Richard Greil, José-Artur Paiva, Thérèse Staub, Evelina Tacconelli, Charles Burdet, Dominique Costagliola, France Mentré, Yazdan Yazdanpanah, Alpha Diallo, DisCoVeRy Study Group, Sandrine Couffin-Cadièrgues, Hélène Espérou, Bernd Lamprecht, Michael Joannidis, Alexander Egle, Richard Greil, Antoine Altdorfer, Vincent Fraipont, Leïla Belkhir, Maya Hites, Gil Verschelden, Violaine Tolsma, David Bougon, Agathe Delbove, Marie Gousseff, Nadia Saïdani, Guilhem Wattecamps, Félix Djossou, Loïc Epelboin, Jean‐Philippe Lanoix, Pierre-Alexandre Roger, Claire Andrejak, Yoann Zerbib, Kévin Bouiller, Catherine Chirouze, Jean-Christophe Navellou, Alexandre Boyer, Charles Cazanave, Alexandre Duvignaud, Didier Gruson, Denis Malvy, Henry Lessire, M. Martinot, Pascal Andreu, Mathieu Blot, Lionel Piroth, Jean‐Pierre Quenot, Olivier Épaulard, Nicolas Terzi, Karine Faure, Emmanuel Faure, Julien Poissy, Saad Nseir, Florence Ader, Laurent Argaud, Tristan Ferry, Thomas Perpoint, Vincent Piriou, Jean‐Christophe Richard, Julien Textoris, Florent Valour, Florent Wallet, André Cabie, Jean-Marie Turmel, Cyrille Chabartier, Rostane Gaci, Céline Robert, Alain Makinson, Vincent Le Moing, Kada Klouche, O. Hinschberger, Joy Mootien, Sébastien Gibot, François Goehringer, Antoine Kimmoun, Benjamin Lefèvre, David Boutoille, Emmanuel Canet, Benjamin Gaborit, Paul Le Turnier, François Raffi, Jean Reignier, Johan Courjon, Jean Dellamonica
Abstract
BACKGROUND: We aimed to evaluate the cardiac adverse events (AEs) in hospitalized patients with coronavirus disease 2019 (COVID-19) who received remdesivir plus standard of care (SoC) compared with SoC alone (control), as an association was noted in some cohort studies and disproportionality analyses of safety databases. METHODS: This post hoc safety analysis is based on data from the multicenter, randomized, open-label, controlled DisCoVeRy trial in hospitalized patients with COVID-19. Any first AE that occurred between randomization and day 29 in the modified intention-to-treat (mITT) population randomized to either remdesivir or control group was considered. Analysis was performed using Kaplan-Meier survival curves, and Kaplan-Meier estimates were calculated for event rates. RESULTS: Cardiac AEs were reported in 46 (11.2%) of 410 and 48 (11.3%) of 423 patients in the mITT population (n = 833) enrolled in the remdesivir and control groups, respectively. The difference between both groups was not significant (hazard ratio [HR], 1.0; 95% confidence interval [CI], .7-1.5; P = .98), even when serious and nonserious cardiac AEs were evaluated separately. The majority of reports in both groups were of arrhythmic nature (remdesivir, 84.8%; control, 83.3%) and were associated with a favorable outcome. There was no significant difference between the two groups in the occurrence of cardiac AE subclasses, including arrhythmic events (HR, 1.1; 95% CI, .7-1.7; P = .68). CONCLUSIONS: Remdesivir treatment was not associated with an increased risk of cardiac AEs compared with control in patients hospitalized with moderate or severe COVID-19. These results are consistent with other randomized, controlled trials and meta-analyses. Clinical Trials Registration. NCT04315948; EudraCT 2020-000936-23.