ABSTRACT
INTRODUCTION: Remdesivir is an antiviral medication that is used in the treatment of severe COVID-19. Research has highlighted the potential cardiac side effects of remdesivir, including the occurrence of remdesivir-associated bradycardia (RAB), but these findings have not been consistent. In addition, very little is known about the clinical implications and outcomes of RAB. The aim of this rapid systematic review is to determine the event rate of developing bradycardia while receiving remdesivir treatment compared with not receiving remdesivir in patients diagnosed with COVID-19. METHODS AND ANALYSIS: This study follows the Preferred Reporting Items for Systematic Review and Meta-Analysis Protocol guidelines and will include original papers related to COVID-19, remdesivir and bradycardia. Only English language papers published from 1 December 2019 to 31 December 2022 will be included. The following databases will be searched using keywords and controlled vocabulary: Ovid MEDLINE, Ovid EMBASE, Scopus, Cochrane, PubMed and Web of Science. Two reviewers will independently perform screening and data abstraction. Data will be synthesised qualitatively as well as quantitatively. A random-effects model will be used to calculate the pooled estimates. ETHICS AND DISSEMINATION: This review will systematically analyse the clinical studies available to help better characterise RAB. The results will support a retrospective study investigating RAB that is currently being conducted at the University Medical Center of Southern Nevada in Las Vegas, Nevada. PROSPERO REGISTRATION NUMBER: This protocol has been submitted to and approved by PROSPERO (Protocol ID: CRD42022331614).
Subject(s)
COVID-19 , Humans , Bradycardia/chemically induced , Retrospective Studies , COVID-19 Drug Treatment , Research Design , Review Literature as Topic , Meta-Analysis as TopicABSTRACT
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.