key: cord-0981548-46jmhn62 authors: Attena, Emilio; Albani, Stefano; Maraolo, Alberto Enrico; Mollica, Mariano; De Rosa, Annunziata; Pisapia, Raffaella; Fiorentino, Giuseppe; Parrella, Roberto; Severino, Sergio; Russo, Vincenzo title: Remdesivir-Induced Bradycardia in COVID-19: A Single Center Prospective Study date: 2021-06-29 journal: Circ Arrhythm Electrophysiol DOI: 10.1161/circep.121.009811 sha: 31de29bda6f22cf2e7df076fcc02122a4154345d doc_id: 981548 cord_uid: 46jmhn62 nan R emdesivir has been recently recognized as a beneficial antiviral therapy for the treatment of hospitalized patients with coronavirus disease 2019 (COVID-19) with lower respiratory tract infection. Cardiac disorders (including atrial fibrillation, supraventricular arrhythmias and other nonspecific arrhythmias) as adverse events occurred in 2.6% of the patients treated with remdesivir. 1 Recently, the occurrence of marked sinus bradycardia has been associated with remdesivir administration. 2 The aim of our single-center prospective observational study was to evaluate the incidence and clinical impact of arrhythmic events in hospitalized patients receiving remdesivir treatment for COVID-19. The data that support the findings of this study are available from the corresponding author upon reasonable request. We prospectively included 166 consecutive laboratory-confirmed COVID-19 patients hospitalized at Cotugno Hospital, Naples-Italy, from September 15 to December 1, 2020, 100 patients received remdesivir treatment according to Italian Medicines Agency indications, 3 66 patients could not be treated with remdesivir due to the late hospital admission (beyond 10 days from the symptoms onset). All patients were treated with azitromicin 500 mg daily for 6 days, dexamethasone 8 to 16 mg per day depending on the severity of the COVID-19 pneumonia and heparin (therapeutic dose if pulmonary embolism was documented). Clinical evaluation, laboratory examinations, and 12 leads ECG were performed before (at hospital admission) and on the fifth day of therapy (from 8 to 11 am). All data are shown in 038 ) was associated to reduced risk of incident sinus bradycardia. The multivariable model could not be performed due to low rate of adverse events. The heart rate reduction (considered as delta heart rate before and after remdesivir administration) was 22 bpm (11.5-31.0, interquartile range) and 9 bpm (0-18.0, interquartile range), in the bradycardia group and in nonbradycardia group, respectively (P=0.001). We performed a sub-analysis in the whole population considering only patients with body temperature <37.2 °C at admission and we still found a significant heart rate reduction after remdesivir was started (from 81 to 70 bpm; P<0.0001). In all cases, sinus bradycardia was reversible at remdesivir discontinuation. No patients were sedated or required blood pressure support during remdesivir treatment. No patients required temporary pacemaker, neither presented hemodynamic instability or ventricular arrhythmias. Patients with sinus bradycardia did not show significant differences in intensive care unit admission rate (9.5% versus 10.1%; P=0.94) and overall mortality (9.5% versus 8.9%; P=0.92) compared with those without remdesivir induced bradycardia. The in-hospital stays were similar between the 2 sub-groups (21.4±6.5 versus 20.3±5.9 days; P=0.48). Remdesivir related incident sinus bradycardia might be due to its status of nucleoside analogue that resembles ATP, justifying its negative reversible chronotropic effect on sinus node cells. 4 According to our findings the incident sinus bradycardia following remdesivir administration did not seem to impact on patients' prognosis in terms of intensive care unit admission and in-hospital mortality. Our results, despite the limitation of potential confounding factors, support a safe use of remdesivir among patients with COVID-19 in a real-world setting. Further studies with larger sample sizes are needed to elucidate the safety profile of remdesivir with regard to cardiovascular events, especially in patients with preexisting arrhythmic disorders. Division of Cardiology, Umberto Parini Hospital ACTT-1 Study Group Members. Remdesivir for the treatment of COVID-19 -Final Report Marked sinus bradycardia associated with remdesivir in COVID-19: a case and literature review Remdesivir nella terapia dei pazienti adulti con COVID-19. 24/11 Remdesivir: review of pharmacology, pre-clinical data, and emerging clinical experience for COVID-19. Pharmacotherapy None. None.