Clinical Characteristics and Implications of Bradycardia in COVID-19 Patients Treated with Remdesivir: A Single-Center Retrospective Cohort Study

Abstract

Background and Objectives Remdesivir is an antiviral drug used to treat coronavirus disease 2019 (COVID-19) with a relatively obscure cardiac effect profile. Previous studies have reported bradycardia associated with remdesivir, but few have examined its clinical characteristics. The objective of this study was to investigate remdesivir associated bradycardia and its associated clinical characteristics and outcomes. Methods This is a single-institution retrospective study that investigated bradycardia in 600 patients who received remdesivir for treatment of COVID-19. A total of 375 patients were included in the study after screening for other known causes of bradycardia (atrioventricular [AV] nodal blockers). All patients were analyzed for episodes of bradycardia from when remdesivir was initiated up to 5 days after completion, a time frame based on the drug’s putative elimination half-life. Univariate and multivariate statistical tests were conducted to analyze the data. Results The mean age of the sample was 56.63 ± 13.23 years. Of patients who met inclusion criteria, 49% were found to have bradycardia within 5 days of remdesivir administration. Compared to the cohort without a documented bradycardic episode, patients with bradycardia were significantly more likely to experience inpatient mortality (22% vs 12%, p = 0.01). The patients with bradycardia were found to have marginally higher serum D-dimer levels (5.2 vs 3.4 µg/mL, p = 0.05) and were more likely to undergo endotracheal intubation (28% vs 14%, p = 0.008). Male sex, hyperlipidemia, and bradycardia within 5 days of completing remdesivir were significant predictors of inpatient mortality. No significant differences in length of stay were found. Conclusions Bradycardia that occurs during or shortly after remdesivir treatment in COVID-19 patients may be associated with an increased rate of in-hospital mortality. However, COVID-19 and its cardiac complications cannot be excluded as potential contributors of bradycardia in the present study. Future studies are needed to further delineate the cardiac characteristics of COVID-19 and remdesivir. Supplementary Information The online version contains supplementary material available at 10.1007/s40261-022-01187-x.

Association of Remdesivir use with bradycardia: A systematic review and meta‐analysis

“…18 The studies included in our analysis indicated that this finding is reversible, 11,12,14 not. 19 The study found a 1.8-fold increase in in-hospital mortality for those who developed bradycardia, and a greater likelihood of requiring mechanical ventilation. In contrast, another study reports that COVID-19 patients who survived had a higher occurrence of bradycardia on Day 5 of Remdesivir treatment than those who deceased.…”

“…The studies included in our analysis indicated that this finding is reversible, 11,12,14 but also demonstrated conflicting results regarding fatal outcomes secondary to bradycardia. One study only included patients who had Remdesivir and compared those who developed bradycardia and those who did not 19 . The study found a 1.8‐fold increase in in‐hospital mortality for those who developed bradycardia, and a greater likelihood of requiring mechanical ventilation.…”

Incidence and potential risk factors for remdesivir-associated bradycardia in hospitalized patients with COVID-19: A retrospective cohort study

“…A study by Pantazopoulos et al included 118 patients who received remdesivir for COVID-19 treatment and found the incidence rate to be bradycardia after remdesivir administration was 40.6% ( Pantazopoulos et al, 2022 ). Another study by Schreiber et al ( Schreiber et al, 2022 ) evaluated 375 patients who experienced bradycardia after remdesivir administration for the treatment of COVID-19 and found the incidence rate to be 49%. Compared to our study, a likely explanation for the higher incidence rate of bradycardia with remdesivir in Schreiber et al ( Schreiber et al, 2022 ) is that they accounted for bradycardia episodes from remdesivir initiation and up to 5 days after remdesivir therapy.…”

“…Another study by Schreiber et al ( Schreiber et al, 2022 ) evaluated 375 patients who experienced bradycardia after remdesivir administration for the treatment of COVID-19 and found the incidence rate to be 49%. Compared to our study, a likely explanation for the higher incidence rate of bradycardia with remdesivir in Schreiber et al ( Schreiber et al, 2022 ) is that they accounted for bradycardia episodes from remdesivir initiation and up to 5 days after remdesivir therapy. Notably, the half-life of remdesivir and its active metabolites is approximately 24 h ( Jorgensen et al, 2020 ).…”

“…Bradycardia can be associated with adverse health outcomes that may lead to impaired functional capacity and provocation of cardiac arrhythmias ( Kusumoto et al, 2019 ). The reported incidence rates of bradycardia associated with remdesivir are inconclusive and vary from 16.8%–49% ( Bistrovic et al, 2022 ; Schreiber et al, 2022 ). In this study, we aim to evaluate the incidence rate, severity, and potential risk factors for the development of bradycardia among hospitalized patients with COVID-19 who received remdesivir.…”