2. Academic Validation
  3. Cardiovascular events and safety outcomes associated with remdesivir using a World Health Organization international pharmacovigilance database

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

  • Clin Transl Sci. 2022 Feb;15(2):501-513. doi: 10.1111/cts.13168.
Se Yong Jung 1,  Min Seo Kim 2 3,  Han Li 4,  Keum Hwa Lee 5,  Ai Koyanagi 6 7 8,  Marco Solmi 9 10 11,  Andreas Kronbichler 12,  Elena Dragioti 13,  Kalthoum Tizaoui 14,  Sarah Cargnin 15,  Salvatore Terrazzino 15,  Sung Hwi Hong 16,  Ramy Abou Ghayda 17,  Nam Kyun Kim 18 19,  Seo Kyoung Chung 20,  Louis Jacob 6 21,  Joe-Elie Salem 22,  Dong Keon Yon 23,  Seung Won Lee 24,  Karel Kostev 25,  Ah Young Kim 1,  Jo Won Jung 1,  Jae Young Choi 1,  Jin Soo Shin 26,  Soon-Jung Park 27,  Seong Woo Choi 28,  Kiwon Ban 29,  Sung-Hwan Moon 27,  Yun Young Go 30,  Jae Il Shin 5,  Lee Smith 31
Affiliations

Affiliations

  • 1 Division of Pediatric Cardiology, Department of Pediatrics, Yonsei University College of Medicine, Seoul, Korea.
  • 2 College of Medicine, Korea University, Seoul, Korea.
  • 3 Samsung Advanced Institute for Health Sciences and Technology (SAIHST), Samsung Medical Center, Sungkyunkwan University, Seoul, Korea.
  • 4 University of Florida College of Medicine, Gainesville, Florida, USA.
  • 5 Department of Pediatrics, Yonsei University College of Medicine, Seoul, Korea.
  • 6 Research and Development Unit, Parc Sanitari Sant Joan de Déu, Universitat de Barcelona, Fundació Sant Joan de Déu, CIBERSAM, Barcelona, Spain.
  • 7 ICREA, Barcelona, Spain.
  • 8 Instituto de Salud Carlos III, Centro de Investigación Biomédica en Red de Salud Mental, CIBERSAM, Madrid, Spain.
  • 9 Department of Psychiatry, University of Ottawa, Ottawa, Ontario, Canada.
  • 10 Department of Mental Health, The Ottawa Hospital, Ottawa, Ontario, Canada.
  • 11 Ottawa Hospital Research Institute (OHRI) Clinical Epidemiology Program, University of Ottawa, Ottawa, Ontario, Canada.
  • 12 Department of Internal Medicine IV, Medical University Innsbruck, Innsbruck, Austria.
  • 13 Department of Health, Medicine and Caring Sciences, Pain and Rehabilitation Centre, Linköping University, Linköping, Sweden.
  • 14 Laboratory Microorganismes and Active Biomolecules, Sciences Faculty of Tunis, Tunis El Manar University, Tunis, Tunisia.
  • 15 Department of Pharmaceutical Sciences, Interdepartmental Research Center of Pharmacogenetics and Pharmacogenomics (CRIFF), University of Piemonte Orientale, Novara, Italy.
  • 16 Yonsei University College of Medicine, Seoul, Korea.
  • 17 Urology Institute, University Hospitals and Case Western Reserve University, Cleveland, Ohio, USA.
  • 18 Department of Pediatrics, Emory University, Atlanta, Georgia, USA.
  • 19 Division of Cardiovascular Surgery, Department of Thoracic and Cardiovascular Surgery, Yonsei University College of Medicine, Seoul, Korea.
  • 20 College of Medicine, Ewha Womans University, Seoul, Korea.
  • 21 Faculty of Medicine, University of Versailles Saint-Quentin-en-Yvelines, Montigny-le-Bretonneux, France.
  • 22 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.
  • 23 Department of Pediatrics, Seoul National University Children's Hospital, Seoul National University College of Medicine, Seoul, Korea.
  • 24 Department of Data Science, Sejong University College of Software Convergence, Seoul, Korea.
  • 25 University Clinic of Marburg, Marburg, Germany.
  • 26 Infectious Disease Research Center, Korea Research Institute of Chemical Technology, Daejeon, Korea.
  • 27 Stem Cell Research Institute, T&R Biofab Co. Ltd, Siheung, Korea.
  • 28 Department of Physiology, Ischemic/Hypoxic Disease Institute, Seoul National University College of Medicine, Seoul, Korea.
  • 29 Department of Biomedical Sciences, City University of Hong Kong, Hong Kong SAR, China.
  • 30 Department of Infectious Diseases and Public Health, City University of Hong Kong, Hong Kong SAR, China.
  • 31 The Cambridge Centre for Sport and Exercise Sciences, Anglia Ruskin University, Cambridge, UK.
PMID: 34719115 DOI: 10.1111/cts.13168
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.

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