Potential Cardiotoxic Effects of Remdesivir on Cardiovascular System: A Literature Review

Abstract

Corona disease 2019 (COVID-19) pandemic continues to spread around the world with no efficacious treatment. Intravenous remdesivir is the only authorized drug for treatment of COVID-19 disease under an Emergency Use Authorization. Remdesivir is a 1′-cyano-substituted adenosine nucleotide prodrug which inhibits viral RNA synthesis. This metabolite is an adenosine analog but with a significantly longer half-life than adenosine. Adenosine is a powerful vasodilator that can cause profound hypotension which is followed by the compensatory release of catecholamines. It can also shorten atrial action potential and refractoriness and lead to atrial fibrillation (AF). These effects may also occur in ventricular cells and predispose patients to ventricular fibrillation. Remdesivir can also induce significant cytotoxic effects in cardiomyocytes that is considerably worse than chloroquine cardiotoxic effects. Remdesivir-induced cardiotoxicity is due to its binding to human mitochondrial RNA polymerase. On the other hand, remdesivir can increase field potential duration with decreased Na + peak amplitudes and spontaneous beating rates in a dose-dependent manner that might induce prolonged QT interval and torsade de point. There are some reports of sinus bradycardia, hypotension, T-wave abnormalities, AF, and a prolonged QT interval and few cases of cardiac arrest and complete heat block following remdesivir infusion. It seems remdesivir have some cardiotoxic and proarrhythmic effects that are especially more pronounced in patients with previous cardiovascular diseases. The current safety profile of remdesivir is still not completely known and further prospective clinical trials are needed to assess its safety profile and potential adverse cardiovascular effects.

Linear mixed model analysis to evaluate correlations between remdesivir adverse effects with age and gender of patients with mild Covid‐19 pneumonia

“…Some Covid‐19 patients on remdesivir may exhibit sinus bradycardia, hypotension, T‐wave abnormalities, and a prolonged QT interval. It has been shown that remdesivir have some cardiotoxic and proarrhythmic effects pronouncedly occur in patients with cardiovascular disorders 10 . Remdesivir is structurally like adenosine but with a longer half‐life.…”

“…9 Regarding cardiovascular complications, sinus bradycardia, hypotension, T-wave abnormalities, atrial fibrillation (AF), and a prolonged QT interval are the most common AEs. 10 It has been shown that remdesivir is adequately tolerated but does not provide significant therapeutic effects in seriously COVID-19 patients. Furthermore, there is a lack of clinical evidence to evaluate the appearance of remdesivir AE and outcomes in men and women and different age groups.…”

Molecular Insights of SARS-CoV-2 Antivirals Administration: A Balance between Safety Profiles and Impact on Cardiovascular Phenotypes

“…Among the most frequent side effects of remdesivir seem to appear anemia, gastrointestinal symptoms, hypertransaminasemia, cutaneous rashes, and kidney injury, other than constitutional local reactions such as infusion-related ones [ 95 ]. Notably, patients may also experience hypotension and cardiac conduction disturbances, as documented by electrocardiographic monitoring.…”

“…Remdesivir can exert an impact on cardiac tissue by inducing electrocardiographic changes such as bradycardia, T-wave abnormalities, atrial fibrillation, and prolonged QT interval [ 95 ]. In addition, a few cases of cardiac arrest were demonstrated following remdesivir infusion.…”

Re: ‘ESCMID COVID-19 living guidelines: drug treatment and clinical management’ by Bartoletti et al

“…Importantly, Bartoletti et al do not mention the severe cardiac side effects associated with RDV use that are now increasingly reported in international pharmacovigilance databases, including cardiac arrest, bradycardia, and hypotension[ 3 , 4 ]. Multiple case reports of bradycardia and other electrocardiogram changes have been reported in the literature following RDV administration[ 5 , 6 ].Mechanisms of RDV-induced cardiotoxicity are not elucidated but might include alterations in the adenosine metabolism[ 5 ] and in vitro data suggest a significant impact of RDV on cell viability of human pluripotent stem cell cardiomyocytes[ 3 ]. The recommendation to use RDV in hospitalized COVID-19 patients should be performed after careful assessment of the benefit-risk balance which has clearly changed since the initial publication of the ACTT-1 trial.…”