REMDESIVIR THERAPY AND ITS ASSOCIATION WITH SINUS BRADYCARDIA

ABSTRACT

TOPIC Chest Infections TYPE Original Investigations PURPOSE: Various case reports have associated transient sinus bradycardia with Remdesivir (RDV) therapy for SARS-CoV2 infection. Pallotto et al., Gubitosa et al., and Touafchia et al. all reported the association of Remdesivir with increased risk of bradycardia in small samples of patients treated with RDV for COVID-19. To our knowledge, no large studies looked at this side effect of RDV therapy. We aimed to analyze the association between sinus bradycardia and Remdesivir therapy for COVID-19. METHODS: A retrospective case-control analysis was done for 1535 patients with SARS-CoV2 infection who were admitted to four teaching hospitals in an urban area in 2020. The mean age was 66 years (SD of 16.7, range 18-99), with 774 males (50.4%). Patients were divided into cases (treated with RDV) and controls (not treated with RDV). Multivariate logistic regression methods were used to analyze the associations between independent variables and outcomes. Pulse rate variables were recorded as pulse rate at day-0, day-3, day-7, and incidence of bradycardia on three consecutive days during admission. Other variables recorded were age, gender, comorbidities, prior history of cardiac disease/arrhythmias, concomitant medications (including AV nodal blockers, dexamethasone, Albuterol, and Lasix), and ICU admission. Survival analysis was run for 7-day and 30-day mortality, as well as survival to hospital discharge. RESULTS: 1415 patients were included in the final analysis, after the exclusion of 120 patients with previous heart blocks. 600 patients (39.1%) were in the Remdesivir group, and 935 patients (60.9%) were in the control group. Between both groups, a total of 454 patients (29.6%) had transient bradycardia on three consecutive days during hospitalization. A multivariate regression analysis was done after adjusting for all confounding variables (age, gender, history of cardiac diseases, AV-nodal blocking drugs, dexamethasone, furosemide, and albuterol therapy). It was seen that there was no statistically significant association between RDV therapy and persistent transient bradycardia (transient bradycardic events on three consecutive days) (Odds Ratio 0.823, 95% confidence interval (CI) 0.594-1.134, p=0.236). There was no statistically significant association of RDV therapy with patients having any bradycardia event during hospitalization in a sub-analysis (Odds Ratio 0.888, 95% confidence interval (CI) 0.665-1.184, p=0.419). Also, RDV failed to show any statistically significant mortality benefit (OR 1.1, CI 0.75-1.62, p=0.6). CONCLUSIONS: Our findings indicate that although transient sinus bradycardia in patients with COVID-19, can be triggered by severe hypoxia, inflammatory damage to AV-nodal cells, or exaggerated response to medications, there was no statistically significant association of RDV therapy with the risk of developing bradycardia. RDV therapy should not be withheld in patients at risk of developing bradycardia. CLINICAL IMPLICATIONS Remdesivir therapy did not increase the risk of developing bradycardia in our patient population. RDV therapy should not be withheld in patients at risk of developing bradycardia. Larger RCTs are needed to validate these findings. DISCLOSURES No relevant relationships by Rahul Bollam, source=Web Response No relevant relationships by Bhagat Kondaveeti, source=Web Response No relevant relationships by Florencio Mamauag, source=Web Response No relevant relationships by Kainat Saleem, source=Web Response No relevant relationships by Manasi Sejpal, source=Web Response No relevant relationships by Megha Sood, source=Web Response No relevant relationships by Morgan Stalder, source=Web Response No relevant relationships by Rosalie Traficante, source=Web Response No relevant relationships by Syed Arsalan Zaidi, source=Web Response