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.
Trial registration: ClinicalTrials.gov NCT04314817 .
【초록키워드】 COVID-19, Treatment, coronavirus disease, Coronavirus disease 2019, Remdesivir, Toxicity, drug, FDA, database, Cardiac arrest, viability, Hypotension, WHO, information, ADRS, cell viability, Adverse drug reaction, food, Adverse drug reactions, bradycardia, Odds ratio, Cardiotoxicity, stem cell, Health Organization, World Health Organization, US Food and Drug Administration, adjusted odds ratio, 95% CI, 95% confidence interval, toxicities, components, confounders, safety margin, physician, Effects, Cell, consequence, performed, reported, approved, conducted, reduced, demonstrated, analysis, maintain, dose-dependent, in vitro experiment, patients with COVID-19, tolerable, 【제목키워드】 outcome, database, cardiovascular, International, event,