Open AccessCardiovascular events and safety outcomes associated with remdesivir using a World Health Organization international pharmacovigilance database
Author(s) -
Jung Se Yong,
Kim Min Seo,
Li Han,
Lee Keum Hwa,
Koyanagi Ai,
Solmi Marco,
Kronbichler Andreas,
Dragioti Elena,
Tizaoui Kalthoum,
Cargnin Sarah,
Terrazzino Salvatore,
Hong Sung Hwi,
Abou Ghayda Ramy,
Kim Nam Kyun,
Chung Seo Kyoung,
Jacob Louis,
Salem JoeElie,
Yon Dong Keon,
Lee Seung Won,
Kostev Karel,
Kim Ah Young,
Jung Jo Won,
Choi Jae Young,
Shin Jin Soo,
Park SoonJung,
Choi Seong Woo,
Ban Kiwon,
Moon SungHwan,
Go Yun Young,
Shin Jae Il,
Smith Lee
Publication year - 2022
Publication title -
clinical and translational science
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.303
H-Index - 44
eISSN - 1752-8062
pISSN - 1752-8054
DOI - 10.1111/cts.13168
Subject(s) - medicine , pharmacovigilance , odds ratio , confidence interval , confounding , covid-19 , adverse effect , pharmacology , emergency medicine , database , disease , computer science , infectious disease (medical specialty)
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.