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

Se Yong Jung; Min Seo Kim; Han Li; Keum Hwa Lee; Ai Koyanagi; Marco Solmi; Andreas Kronbichler; Elena Dragioti; Kalthoum Tizaoui; Sarah Cargnin; Salvatore Terrazzino; Sung Hwi Hong; Ramy Abou Ghayda; Nam Kyun Kim; Seo Kyoung Chung; Louis Jacob; Joe Elie Salem; Dong Keon Yon; Seung Won Lee; Karel Kostev; Ah Young Kim; Jo Won Jung; Jae Young Choi; Jin Soo Shin; Soon Jung Park; Seong Woo Choi; Kiwon Ban; Sung Hwan Moon; Yun Young Go; Jae Il Shin; Lee Smith

doi:10.1111/cts.13168

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

Se Yong Jung, Min Seo Kim, Han Li, Keum Hwa Lee, Ai Koyanagi, Marco Solmi, Andreas Kronbichler, Elena Dragioti, Kalthoum Tizaoui, Sarah Cargnin, Salvatore Terrazzino, Sung Hwi Hong, Ramy Abou Ghayda, Nam Kyun Kim, Seo Kyoung Chung, Louis Jacob, Joe Elie Salem, Dong Keon Yon, Seung Won Lee, Karel KostevAh Young Kim, Jo Won Jung, Jae Young Choi, Jin Soo Shin, Soon Jung Park, Seong Woo Choi, Kiwon Ban, Sung Hwan Moon, Yun Young Go, Jae Il Shin, Lee Smith

Department of Pediatrics

Research output: Contribution to journal › Article › peer-review

9 Citations (Scopus)

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.

Original language	English
Pages (from-to)	501-513
Number of pages	13
Journal	Clinical and Translational Science
Volume	15
Issue number	2
DOIs	https://doi.org/10.1111/cts.13168
Publication status	Published - 2022 Feb

Bibliographical note

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.

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. The authors appreciate members of the custom search team at the Uppsala Monitoring Centre (Uppsala, Sweden) research section, who were invaluable to the successful performance of this study. The supplied data from VigiBase was obtained from various sources and the likelihood of a causal relationship was not the same in all reports. Finally, the results and conclusions of this study do not represent the opinion of the WHO.

Publisher Copyright:
© 2021 The Authors. Clinical and Translational Science published by Wiley Periodicals LLC on behalf of American Society for Clinical Pharmacology and Therapeutics.

All Science Journal Classification (ASJC) codes

Neuroscience(all)
Biochemistry, Genetics and Molecular Biology(all)
Pharmacology, Toxicology and Pharmaceutics(all)

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

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10.1111/cts.13168

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Jung, S. Y., Kim, M. S., Li, H., Lee, K. H., Koyanagi, A., Solmi, M., Kronbichler, A., Dragioti, E., Tizaoui, K., Cargnin, S., Terrazzino, S., Hong, S. H., Abou Ghayda, R., Kim, N. K., Chung, S. K., Jacob, L., Salem, J. E., Yon, D. K., Lee, S. W., ... Smith, L. (2022). Cardiovascular events and safety outcomes associated with remdesivir using a World Health Organization international pharmacovigilance database. Clinical and Translational Science, 15(2), 501-513. https://doi.org/10.1111/cts.13168

@article{4d2e3f0976c4486b862398f513f487ba,

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

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.",

author = "Jung, {Se Yong} and Kim, {Min Seo} and Han Li and Lee, {Keum Hwa} and Ai Koyanagi and Marco Solmi and Andreas Kronbichler and Elena Dragioti and Kalthoum Tizaoui and Sarah Cargnin and Salvatore Terrazzino and Hong, {Sung Hwi} and {Abou Ghayda}, Ramy and Kim, {Nam Kyun} and Chung, {Seo Kyoung} and Louis Jacob and Salem, {Joe Elie} and Yon, {Dong Keon} and Lee, {Seung Won} and Karel Kostev and Kim, {Ah Young} and Jung, {Jo Won} and Choi, {Jae Young} and Shin, {Jin Soo} and Park, {Soon Jung} and Choi, {Seong Woo} and Kiwon Ban and Moon, {Sung Hwan} and Go, {Yun Young} and Shin, {Jae Il} and Lee Smith",

note = "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. 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. The authors appreciate members of the custom search team at the Uppsala Monitoring Centre (Uppsala, Sweden) research section, who were invaluable to the successful performance of this study. The supplied data from VigiBase was obtained from various sources and the likelihood of a causal relationship was not the same in all reports. Finally, the results and conclusions of this study do not represent the opinion of the WHO. Publisher Copyright: {\textcopyright} 2021 The Authors. Clinical and Translational Science published by Wiley Periodicals LLC on behalf of American Society for Clinical Pharmacology and Therapeutics.",

year = "2022",

month = feb,

doi = "10.1111/cts.13168",

language = "English",

volume = "15",

pages = "501--513",

journal = "Clinical and Translational Science",

issn = "1752-8054",

publisher = "Wiley-Blackwell",

number = "2",

}

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 & Smith, L 2022, 'Cardiovascular events and safety outcomes associated with remdesivir using a World Health Organization international pharmacovigilance database', Clinical and Translational Science, vol. 15, no. 2, pp. 501-513. https://doi.org/10.1111/cts.13168

TY - JOUR

T1 - Cardiovascular events and safety outcomes associated with remdesivir using a World Health Organization international pharmacovigilance database

AU - Jung, Se Yong

AU - Kim, Min Seo

AU - Li, Han

AU - Lee, Keum Hwa

AU - Koyanagi, Ai

AU - Solmi, Marco

AU - Kronbichler, Andreas

AU - Dragioti, Elena

AU - Tizaoui, Kalthoum

AU - Cargnin, Sarah

AU - Terrazzino, Salvatore

AU - Hong, Sung Hwi

AU - Abou Ghayda, Ramy

AU - Kim, Nam Kyun

AU - Chung, Seo Kyoung

AU - Jacob, Louis

AU - Salem, Joe Elie

AU - Yon, Dong Keon

AU - Lee, Seung Won

AU - Kostev, Karel

AU - Kim, Ah Young

AU - Jung, Jo Won

AU - Choi, Jae Young

AU - Shin, Jin Soo

AU - Park, Soon Jung

AU - Choi, Seong Woo

AU - Ban, Kiwon

AU - Moon, Sung Hwan

AU - Go, Yun Young

AU - Shin, Jae Il

AU - Smith, Lee

N1 - 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. 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. The authors appreciate members of the custom search team at the Uppsala Monitoring Centre (Uppsala, Sweden) research section, who were invaluable to the successful performance of this study. The supplied data from VigiBase was obtained from various sources and the likelihood of a causal relationship was not the same in all reports. Finally, the results and conclusions of this study do not represent the opinion of the WHO. Publisher Copyright: © 2021 The Authors. Clinical and Translational Science published by Wiley Periodicals LLC on behalf of American Society for Clinical Pharmacology and Therapeutics.

PY - 2022/2

Y1 - 2022/2

N2 - 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.

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

Abstract

Bibliographical note

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UN SDGs

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