Persistent Bradycardia May Occur After Remdesivir Infusion in Patients With COVID-19

Results of a study published in JAMA Network Open indicate a relationship between bradycardia and remdesivir infusion in the setting of COVID-19 infection.

The FACT Pharmacovigilance Project is an ongoing surveillance program designed to evaluate adverse outcomes from nonvaccine-related treatments for COVID-19 infection, with data source from 15 medical centers in the United States. For this study, patients (N=188) who had a pulse of more than 60/min within 24 hours of remdesivir administration were evaluated to determine the duration and potential risk factors for bradycardic events. Researchers used linear mixed-effects models to assess the minimum pulse prior to remdesivir receipt and within 24 hours of each subsequent dose, with doses considered fixed effects. Baseline covariates, including age (≥65 vs <65 years), sex at birth, and positive vs negative cardiovascular history, were used to adjust and identify effect modifications.

Among patients included in the analysis, the mean (SD) age was 61.3 (15.4) years, 57.4% were men, 39.9% were White, 71.3% had a positive cardiovascular history, and 36.7% had obesity.

Most patients (72.3%) received 5 doses of remdesivir and 4.8% received additional doses due to lack of symptom improvement or critical illness; the remaining 22.9% of patients received less than 5 doses. Infusion-associated bradycardia was observed among 45 patients, all of whom experienced continued bradycardia outside the infusion period.

There were 109 (58%) and 79 (42.0%) severe and nonsevere adverse events, respectively, reported among the patients. Of 69 patients who experienced potentially life-threatening events, 36.7% had a pulse of £45/min, 1.1% had QRS and/or QTc prolongation, 1.1% had cardiac arrest, 0.5% had sinus pause, and 0.5% had ventricular tachycardia.

Few patients received interventions for bradycardia, but the most common were remdesivir discontinuation (n=10) and intensive care unit transfer (n=9).

The median time to first bradycardic event was 23.4 hours. This time was significantly shorter for patients aged 65 years and older vs those older than 65 (median, 18.7 vs 31.5 hours; P =.04), respectively, especially among those 65 years and older with a positive cardiovascular history (median, 17.7 hours; P =.05).

The lowest mean pulse was 55.6/min, and the median time to lowest pulse was 60.7 hours. The time to lowest pulse was shorter among men compared with women (median, 54.2 vs 71.0 hours, respectively; P =.02). Time to lowest heart rate did significantly differ on the basis only age (χ², 1.22; P =.27), only cardiovascular history (χ², 1.61; P =.20), or both age and cardiovascular history (χ², 4.72; P =.19).

This study may have been limited by selection bias and the lack of a control cohort.

According to the researchers, “Given the widespread use of remdesivir in COVID-19, practitioners should be aware of the potential for delayed-onset or sustained bradycardia.”