Remdesivir Safe in COVID-19 Patients, Despite Risk of Sinus Bradycardia

By Lorraine L. Janeczko

July 15, 2021

NEW YORK (Reuters Health) - Remdesivir treatment of lower respiratory infection in hospitalized patients with COVID-19 appears safe, even though some patients develop sinus bradycardia, a single-center prospective study from Italy suggests.

"Cardiac disorders (including atrial fibrillation, supraventricular arrhythmias and other nonspecific arrhythmias) as adverse events occurred in 2.6% of the patients treated with remdesivir," the study authors write in Circulation: Arrhythmia and Electrophysiology. "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."

Dr. Emilio Attena of Cotugno Hospital in Naples and colleagues evaluated 166 consecutive hospitalized patients treated for COVID-19 with remdesivir at one hospital between September 15 and December 1, 2020. One hundred patients received remdesivir treatment, and 66 were not treated with the drug because they were admitted to the hospital more than 10 days from symptom onset.

At baseline, the remdesivir and the control groups had similar clinical characteristics, except for D-dimer value (216 vs. 274 ng/mL, respectively; P=0.03).

All patients were treated with azithromycin 500 mg daily for six days, dexamethasone 8 to 16 mg per day, and a therapeutic dose of heparin if pulmonary embolism was found. Clinical examinations, laboratory tests, and twelve-lead electrocardiograms were performed at admission and on the morning of the fifth day of treatment.

On the fifth day, 21% of patients in the remdesivir group and 3% of controls had sinus bradycardia (P=0.001); PaO2/FiO2 values in the remdesivir group were 313 and 213 among controls (P=0.0001).

Overall, 29% of patients who received remdesivir and had sinus bradycardia were female, compared to 10% of those who received remdesivir and did not have bradycardia (P=0.03).

At day 5, patients on remdesivir who developed bradycardia had a lower resting heart rate than those on remdesivir who did not develop bradycardia (53 vs. 76 beats per minute; P=0.0001). They also had a higher D-dimer value (395 vs. 180 ng/mL; P=0.008).

In all patients, sinus bradycardia stopped when remdesivir was withdrawn.

Patients treated with remdesivir were hospitalized for around 21 days, whether or not they experienced bradycardia. Those on remdesivir with or without sinus bradycardia had similar rates of admission to the intensive-care unit (9.5% vs. 10.1% respectively) and overall mortality (9.5% vs. 8.9% respectively).

"For patients with COVID-19 treated with remdesivir, the drop in heart rate did not appear to cause any adverse outcomes," Dr. Denice Hodgson-Zingman, who was not involved in the study, told Reuters Health by email. "But one might imagine that its use could be problematic in someone already known to have a slow heart rate at baseline, or who is prone to slow heart rate due to other medications or conditions."

"The proposed potential mechanism for the bradycardia is the similarity of remdesivir to ATP and adenosine that are known to have direct and indirect cardiac slowing and other cardiac electrophysiologic effects," Dr. Hodgson-Zingman, a professor of internal and cardiovascular medicine, and the director of cardiac electrophysiology at University of Iowa Health Care in Iowa City, noted.

"The impact of remdesivir on other components of the cardiac conduction system were not explored here, but further studies may identify abnormal cardiac rate and rhythm conditions in which remdesivir could be clinically useful or detrimental," she added. "I'm eager to see this phenomenon explored in more depth in follow-on studies and plan to watch my vulnerable patients closely for otherwise unexplained bradycardia."

Dr. Kevin S. Shah, a cardiologist and assistant professor at University of Utah Health in Salt Lake City, said this case series adds to other published case reports about this finding.

"This helpful case series demonstrates that bradycardia is a common side effect, but fortunately seems well-tolerated, and it supports the safety of remdesivir," Dr. Shah, who was not involved in the study, told Reuters Health by email.

"Patients receiving this drug should have their heart rates monitored continuously while in the hospital," he advised.

"The study's strengths include that this is 'real-world' data, while its weaknesses include the fact that the study is from a single center in Italy."

The corresponding author did not respond to requests for comment.

The study did not receive commercial funding. The authors and Drs. Shah and Hodgson-Zingman declared no conflicts of interest.

SOURCE: Circulation: Arrhythmia and Electrophysiology, online June 29, 2021.