Cardiovascular events and safety outcomes associated with remdesivir using a World Health Organization international pharmacovigilance database

• Type of Material: Article
• Authors: Se Yong Jung, Yonsei University; Min Seo Kim, Korea University; Han Li, University of Florida; Keum Hwa Lee, Yonsei University; Ai Koyanagi, University of Barcelona; Marco Solmi, University of Ottawa; Andreas Kronbichler, Medical University of Innsbruck; Elena Dragioti, Linkoping University; Kalthoum Tizaoui, Tunis El Manar Univ; Sarah Cargnin, University of Piemonte Orientale; Salvatore Terrazzino, University of Piemonte Orientale; Sung H Hong, Yonsei University; Ramy Abou Ghayda ggg, University Hospitals and Case Western Reserve University; Nam Kyun Kim, Emory University; Seo Kyoung Chung, Ewha Womans University; Louis Jacob, University of Barcelona; Joe-Elie Salem, Sorbonne Universite; Dong Keon Yon, Seoul National University; Seung Won Lee, Sejong University; Karel Kostev, University Clinic of Marburg; Ah Young Kim, Yonsei University; Jo Won Jung, Yonsei University; Jae Y Choi, Yonsei University; Jin Soo Shin, Korea Research Institute of Chemical Technology; Soon-Jung Park, T&R Biofab Co. Ltd; Seong Woo Choi, Seoul National University; Kiwon Ban, City University of Hong Kong; Sung-Hwan Moon, T&R Biofab Co. Ltd; Yun Young Go, City University of Hong Kong; Lee Smith, Anglia Ruskin University
• Language: English
• Date: 2021-10-31
• Publisher: WILEY
• Publication Version: Final Published Version
• Copyright Statement: © 2021 The Authors. Clinical and Translational Science published by Wiley Periodicals LLC on behalf of American Society for Clinical Pharmacology and Therapeutics.
• License: Creative Commons Attribution-NonCommercial 4.0 International
• Final Published Version (URL): http://dx.doi.org/10.1111/cts.13168
• Title of Journal or Parent Work: CTS-CLINICAL AND TRANSLATIONAL SCIENCE
• Volume: 15
• Issue: 2
• Start Page: 501
• End Page: 513
• Grant/Funding Information: This study was supported by a new faculty research seed money grant of Yonsei University College of Medicine for 2021 (2021‐32‐0049). The funders had no role in the design, analyses, or interpretation of the study.
• Keywords: Medicine, Research & Experimental; Science & Technology; VIGIBASE; COVID-19; Research & Experimental Medicine; Life Sciences & Biomedicine
• Research Categories: Health Sciences, Medicine and Surgery; Health Sciences, Pharmacy

Abstract

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.