Cardiovascular events and safety outcomes associated with remdesivir using a World Health Organization international pharmacovigilance database.
Por:
Jung SY, Kim MS, Li H, Lee KH, Koyanagi A, Solmi M, Kronbichler A, Dragioti E, Tizaoui K, Cargnin S, Terrazzino S, Hong SH, Abou Ghayda R, Kim NK, Chung SK, Jacob L., Salem JE, Yon DK, Lee SW, Kostev K, Kim AY, Jung JW, Choi JY, Shin JS, Park SJ, Choi SW, Ban K, Moon SH, Go YY, Shin JI and Smith L
Publicada:
1 feb 2022
Ahead of Print:
31 oct 2021
Resumen:
On October 2020, the US Food and Drug Administration (FDA) approved remdesivir as the first drug for the treatment of coronavirus disease 2019 (COVID-19), increasing remdesivir prescriptions worldwide. However, potential cardiovascular (CV) toxicities associated with remdesivir remain unknown. We aimed to characterize the CV adverse drug reactions (ADRs) associated with remdesivir using VigiBase, an individual case safety report database of the World Health Organization (WHO). Disproportionality analyses of CV-ADRs associated with remdesivir were performed using reported odds ratios and information components. We conducted in vitro experiments using cardiomyocytes derived from human pluripotent stem cell cardiomyocytes (hPSC-CMs) to confirm cardiotoxicity of remdesivir. To distinguish drug-induced CV-ADRs from COVID-19 effects, we restricted analyses to patients with COVID-19 and found that, after adjusting for multiple confounders, cardiac arrest (adjusted odds ratio [aOR]: 1.88, 95% confidence interval [CI]: 1.08-3.29), bradycardia (aOR: 2.09, 95% CI: 1.24-3.53), and hypotension (aOR: 1.67, 95% CI: 1.03-2.73) were associated with remdesivir. In vitro data demonstrated that remdesivir reduced the cell viability of hPSC-CMs in time- and dose-dependent manners. Physicians should be aware of potential CV consequences following remdesivir use and implement adequate CV monitoring to maintain a tolerable safety margin.
Filiaciones:
Jung SY:
Division of Pediatric Cardiology, Department of Pediatrics, Yonsei University College of Medicine, Seoul, Korea
Kim MS:
College of Medicine, Korea University, Seoul, Korea
Samsung Advanced Institute for Health Sciences and Technology (SAIHST), Samsung Medical Center, Sungkyunkwan University, Seoul, Korea
Li H:
University of Florida College of Medicine, Gainesville, Florida, USA
Lee KH:
Department of Pediatrics, Yonsei University College of Medicine, Seoul, Korea
Koyanagi A:
Research and Development Unit, Parc Sanitari Sant Joan de Déu, Universitat de Barcelona, Fundació Sant Joan de Déu, CIBERSAM, Barcelona, Spain
ICREA, Barcelona, Spain
Instituto de Salud Carlos III, Centro de Investigación Biomédica en Red de Salud Mental, CIBERSAM, Madrid, Spain
Solmi M:
Department of Psychiatry, University of Ottawa, Ottawa, Ontario, Canada
Department of Mental Health, The Ottawa Hospital, Ottawa, Ontario, Canada
Ottawa Hospital Research Institute (OHRI) Clinical Epidemiology Program, University of Ottawa, Ottawa, Ontario, Canada
Kronbichler A:
Department of Internal Medicine IV, Medical University Innsbruck, Innsbruck, Austria
Dragioti E:
Department of Health, Medicine and Caring Sciences, Pain and Rehabilitation Centre, Linköping University, Linköping, Sweden
Tizaoui K:
Laboratory Microorganismes and Active Biomolecules, Sciences Faculty of Tunis, Tunis El Manar University, Tunis, Tunisia
Cargnin S:
Department of Pharmaceutical Sciences, Interdepartmental Research Center of Pharmacogenetics and Pharmacogenomics (CRIFF), University of Piemonte Orientale, Novara, Italy
Terrazzino S:
Department of Pharmaceutical Sciences, Interdepartmental Research Center of Pharmacogenetics and Pharmacogenomics (CRIFF), University of Piemonte Orientale, Novara, Italy
Hong SH:
Yonsei University College of Medicine, Seoul, Korea
Abou Ghayda R:
Urology Institute, University Hospitals and Case Western Reserve University, Cleveland, Ohio, USA
Kim NK:
Department of Pediatrics, Emory University, Atlanta, Georgia, USA
Division of Cardiovascular Surgery, Department of Thoracic and Cardiovascular Surgery, Yonsei University College of Medicine, Seoul, Korea
Chung SK:
College of Medicine, Ewha Womans University, Seoul, Korea
Jacob L.:
Research and Development Unit, Parc Sanitari Sant Joan de Déu, Universitat de Barcelona, Fundació Sant Joan de Déu, CIBERSAM, Barcelona, Spain
Faculty of Medicine, University of Versailles Saint-Quentin-en-Yvelines, Montigny-le-Bretonneux, France
Salem JE:
Department of Pharmacology, INSERM, CIC-1901 Paris-Est, CLIP Galilée, UNICO-GRECO Cardio-oncology Program, Pitié-Salpêtrière Hospital, Assistance Publique-Hôpitaux de Paris, Sorbonne Université, Paris, France
Yon DK:
Department of Pediatrics, Seoul National University Children's Hospital, Seoul National University College of Medicine, Seoul, Korea
Lee SW:
Department of Data Science, Sejong University College of Software Convergence, Seoul, Korea
Kostev K:
University Clinic of Marburg, Marburg, Germany
Kim AY:
Division of Pediatric Cardiology, Department of Pediatrics, Yonsei University College of Medicine, Seoul, Korea
Jung JW:
Division of Pediatric Cardiology, Department of Pediatrics, Yonsei University College of Medicine, Seoul, Korea
Choi JY:
Division of Pediatric Cardiology, Department of Pediatrics, Yonsei University College of Medicine, Seoul, Korea
Shin JS:
Infectious Disease Research Center, Korea Research Institute of Chemical Technology, Daejeon, Korea
Park SJ:
Stem Cell Research Institute, T&R Biofab Co. Ltd, Siheung, Korea
Choi SW:
Department of Physiology, Ischemic/Hypoxic Disease Institute, Seoul National University College of Medicine, Seoul, Korea
Ban K:
Department of Biomedical Sciences, City University of Hong Kong, Hong Kong SAR, China
Moon SH:
Stem Cell Research Institute, T&R Biofab Co. Ltd, Siheung, Korea
Go YY:
Department of Infectious Diseases and Public Health, City University of Hong Kong, Hong Kong SAR, China
Shin JI:
Department of Pediatrics, Yonsei University College of Medicine, Seoul, Korea
Smith L:
The Cambridge Centre for Sport and Exercise Sciences, Anglia Ruskin University, Cambridge, UK
Green Accepted, Green Published
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