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

Abstract

Background: Remdesivir is widely used for the management of COVID-19 and several studies have reported bradycardia as a potential side effect associated with this agent. The aim of the present study was to evaluate the incidence rate, severity, and potential risk factors of remdesivir-associated bradycardia.Methods: We performed a retrospective cohort study among hospitalized adult patients with COVID-19 who were treated with remdesivir from March 2020 to October 2021. Our primary outcome of interest was the incidence rate and severity of bradycardia after remdesivir administration. We defined mild bradycardia as a heart rate of 51–59 beats per minute, moderate bradycardia as a heart rate of 41–50 beats per minute, and severe bradycardia as a heart rate of ≤40 beats per minute. We also performed univariable and multivariable regression analyses to determine potential bradycardia risk factors. Baseline characteristics were reported as means with standard deviations or medians with interquartile ranges (IQRs). All the statistical tests are shown as odds ratios (ORs) with 95% confidence intervals (CIs).Results: In total, 1,635 patients were included in this study. The median age with IQR was 68 (57–79) years and 51.7% of the patients were male. In total, 606 (37.1%) patients developed bradycardia. Among them, 437 patients (26.7%) developed mild bradycardia, 158 patients (9.7%) moderate bradycardia, while 11 patients (0.7%) experienced severe bradycardia. In our adjusted multivariate logistic regression, the odds of bradycardia development after remdesivir administration were higher among patients with age ≥65 years (OR 1.76, 95% CI: 1.04–2.99, p = 0.04), those with hypertension (OR 1.37, 95% CI: 1.07–1.75, p = 0.01), and obesity (OR 1.32, 95% CI: 1.02–1.68, p = 0.03).Conclusion: More than 1 out of 3 patients (37%) who received remdesivir for COVID-19 developed bradycardia with the majority of these patients developing mild or moderate bradycardia that is usually a benign manifestation not needing treatment in most cases. Age ≥65 years, hypertension, and obesity were potential risk factors for remdesivir-associated bradycardia among hospitalized COVID-19 patients. Clinicians should be aware of this adverse event and consider close clinical monitoring for patients at high risk for this adverse event.

Remdesivir-Induced Bradycardia and Mortality in SARS-CoV-2 Infection, Potential Risk Factors Assessment: A Systematic Review and Meta-Analysis

“…Additionally, w examined the risk factors associated with remdesivir-induced bradycardia. Our meta-analysis was comprised of ten retrospective studies and two prospective studies, involving a total of 7674 adult individuals [16][17][18][19][20][21][22][23][24][25][26][27]. All included studies were conducted in adult populations.…”

“…Forest plot of remdesivir-induced bradycardia associated with chronic kidney disease (CKD) [23,26,27]. (CVDs), hypertension, diabetes, thyroid disease, chronic kidney disease (CKD), intensive care unit (ICU) admission, and beta-blocker or antiarrhythmic drug usage.…”

“…Figure 7. Forest plot of remdesivir-induced bradycardia associated with chronic kidney disease (CKD) [23,26,27]. Regarding the assessment of sex (OR = 0.998, 95% CI = 0.811-1.228, p = 0.982, I 2 = 38.04%, Egger's p = 0.380), age (OR = 0.286, 95% CI = −0.154-0.725, p = 0.202, I 2 = 94.16%, Egger's p = 0.157), CVDs (OR = 0.977, 95% CI = 0.751-1.271, p = 0.861, I 2 = 30.66%, Egger's p = 0.932), hypertension (OR = 1.253, 95% CI = 0.935-1.679, p = 0.131, I 2 = 32.29%, Egger's p = 0.133), diabetes (OR = 0.928, 95% CI = 0.770-1.118, p = 0.430, I 2 = 0.0%, Egger's p = 0.555), thyroid disease (OR = 1.344, 95% CI = 0.984-1.835, p = 0.063, I 2 = 0.0%, Egger's p = 0.474), ICU admission (OR = 1.080, 95% CI = 0.612-1.905, p = 0.791, I 2 = 83.66%, Egger's p = 0.429), and beta-blocker (OR = 1.038, 95% CI = 0.779-1.382, p = 0.801, I 2 = 0.0%, Egger's p = 0.973) or antiarrhythmic drug usage (OR = 0.814, 95% CI = 0.125-5.288, p = 0.829, I 2 = 70.68%, Egger's p = 0.573), all results indicated no significant difference between the remdesivir-induced bradycardia and bradycardia-free groups (Figures S2-S10).…”

“…Figure 7. Forest plot of remdesivir-induced bradycardia associated with chronic kidney disease (CKD)[23,26,27].…”

Efficacy and Safety of Remdesivir in Hospitalized Pediatric COVID-19: A Retrospective Case-Controlled Study

“…Limited data on children are accessible, given that the majority of clinical trials have concentrated on adults. 21,31,[36][37][38][39][40][41] Due to well-established physiological differences between adults and children, any drug that proves effective in treating adults might not be appropriate for pediatric use. Furthermore, there is currently a lack of information on the pediatric pharmacokinetics of RDV exposure.…”