Remdesivir, favipiravir may not be heart-friendly
Remdesivir and favipiravir does not appear to be heart-friendly in patients with COVID-19, according to a study presented at APSR 2023.
“Our study results show that remdesivir and favipiravir have some cardiotoxic and pro-arrhythmic effects when administered in patients with moderate-to-severe COVID-19,” said Dr Kristin Purnama Dewi from the Faculty of Medicine, Airlangga University, Surabaya, Indonesia, who presented the findings at APSR 2023.
Of the 301 patients who tested positive for COVID-19 via RT-PCR testing, 180 met the eligibility criteria (mean age 56.96 years, 56.7 percent male). These patients were hospitalized for moderate-to-severe disease and were retrospectively evaluated. Of these, 125 were treated with favipiravir (1,600 mg BID on day 1 followed by 600 mg BID) while the remaining 55 were on remdesivir treatment (200 mg loading dose followed by 100 mg QD). Almost all (96 percent) patients on remdesivir had severe disease. For those who received favipiravir, 87 percent had moderate disease. [APSR 2023, abstract AO07-6]
Among those on remdesivir, 29 percent were hypertensive and roughly 13 percent had hypotensive events. Seven percent had prolonged QT interval. The rates of bradycardia, tachycardia, and atrial fibrillation were 9, 18, and 16 percent, respectively.
Remdesivir-induced cardiotoxicities could be due to binding to human mitochondrial RNA polymerase, noted Dewi. “Remdesivir is a 1-cyano-substituted adenosine nucleotide prodrug … Adenosine is a powerful vasodilator that can cause profound hypotension,” she added. [Cardiovasc Toxicol 2022;22:268-272; Curr Probl Cardiol 2020;45:100617]
For those on favipiravir, 23 percent had hypertension and 4 percent had hypotension. Nearly 20 percent had prolonged QT interval, which is nearly threefold than that reported in the remdesivir subgroup. For bradycardia, tachycardia and atrial fibrillation, the corresponding rates were 5, 19, and 10 percent.
Favipiravir increases glutathione levels causing oxidative stress, noted Dewi. This, in turn, causes DNA damage in cardiomyoblasts that consequently leads to cardiotoxicities. The increased rates of tachycardia and prolonged QTc with favipiravir observed in the current study also align with prior evidence. [Infect Drug Resist 2020:13:4427-4438; Eur Heart J Acute Cardiovasc Care 2020;9:215-221] “However, the mechanism [that could explain] how favipiravir induces prolonged QTc is still not fully understood,” she noted.
There were no significant differences in terms of 30-day mortality between those on remdesivir and favipiravir (hazard ratio, 0.51, 95 percent confidence interval, 0.25–1.30; p=0.061).
Despite the reported therapeutic benefits of remdesivir and favipiravir against COVID-19, it is important to consider the cardiovascular side effects of both agents, underlined Dewi. [Cardiovasc Hematol Disord Drug Targets 2021;21:88-90]
Dewi identified two main mechanisms that could account for the observed remdesivir- and favipiravir-induced cardiotoxicities: DNA damage and increased oxidative stress. She called for further studies with larger sample sizes to validate the cardiovascular safety of both COVID-19 antivirals.