tetano
Editor, Senior Moderator
Clin Transl Sci
. 2021 Oct 31.
doi: 10.1111/cts.13168. Online ahead of print.
Cardiovascular events and safety outcomes associated with remdesivir using a World Health Organization international pharmacovigilance database
Se Yong Jung[SUP] 1 [/SUP], Min Seo Kim[SUP] 2 3 [/SUP], Han Li[SUP] 4 [/SUP], Keum Hwa Lee[SUP] 5 [/SUP], Ai Koyanagi[SUP] 6 7 8 [/SUP], Marco Solmi[SUP] 9 10 11 [/SUP], Andreas Kronbichler[SUP] 12 [/SUP], Elena Dragioti[SUP] 13 [/SUP], Kalthoum Tizaoui[SUP] 14 [/SUP], Sarah Cargnin[SUP] 15 [/SUP], Salvatore Terrazzino[SUP] 15 [/SUP], Sung Hwi Hong[SUP] 16 [/SUP], Ramy Abou Ghayda[SUP] 17 [/SUP], Nam Kyun Kim[SUP] 18 19 [/SUP], Seo Kyoung Chung[SUP] 20 [/SUP], Louis Jacob[SUP] 6 21 [/SUP], Joe-Elie Salem[SUP] 22 [/SUP], Dong Keon Yon[SUP] 23 [/SUP], Seung Won Lee[SUP] 24 [/SUP], Karel Kostev[SUP] 25 [/SUP], Ah Young Kim[SUP] 1 [/SUP], Jo Won Jung[SUP] 1 [/SUP], Jae Young Choi[SUP] 1 [/SUP], Jin Soo Shin[SUP] 26 [/SUP], Soon-Jung Park[SUP] 27 [/SUP], Seong Woo Choi[SUP] 28 [/SUP], Kiwon Ban[SUP] 29 [/SUP], Sung-Hwan Moon[SUP] 27 [/SUP], Yun Young Go[SUP] 30 [/SUP], Jae Il Shin[SUP] 5 [/SUP], Lee Smith[SUP] 31 [/SUP]
Affiliations
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.
. 2021 Oct 31.
doi: 10.1111/cts.13168. Online ahead of print.
Cardiovascular events and safety outcomes associated with remdesivir using a World Health Organization international pharmacovigilance database
Se Yong Jung[SUP] 1 [/SUP], Min Seo Kim[SUP] 2 3 [/SUP], Han Li[SUP] 4 [/SUP], Keum Hwa Lee[SUP] 5 [/SUP], Ai Koyanagi[SUP] 6 7 8 [/SUP], Marco Solmi[SUP] 9 10 11 [/SUP], Andreas Kronbichler[SUP] 12 [/SUP], Elena Dragioti[SUP] 13 [/SUP], Kalthoum Tizaoui[SUP] 14 [/SUP], Sarah Cargnin[SUP] 15 [/SUP], Salvatore Terrazzino[SUP] 15 [/SUP], Sung Hwi Hong[SUP] 16 [/SUP], Ramy Abou Ghayda[SUP] 17 [/SUP], Nam Kyun Kim[SUP] 18 19 [/SUP], Seo Kyoung Chung[SUP] 20 [/SUP], Louis Jacob[SUP] 6 21 [/SUP], Joe-Elie Salem[SUP] 22 [/SUP], Dong Keon Yon[SUP] 23 [/SUP], Seung Won Lee[SUP] 24 [/SUP], Karel Kostev[SUP] 25 [/SUP], Ah Young Kim[SUP] 1 [/SUP], Jo Won Jung[SUP] 1 [/SUP], Jae Young Choi[SUP] 1 [/SUP], Jin Soo Shin[SUP] 26 [/SUP], Soon-Jung Park[SUP] 27 [/SUP], Seong Woo Choi[SUP] 28 [/SUP], Kiwon Ban[SUP] 29 [/SUP], Sung-Hwan Moon[SUP] 27 [/SUP], Yun Young Go[SUP] 30 [/SUP], Jae Il Shin[SUP] 5 [/SUP], Lee Smith[SUP] 31 [/SUP]
Affiliations
- 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.