Association of Remdesivir use with bradycardia: A systematic review and meta‐analysis

Abstract

Remdesivir has been used for coronavirus disease 2019 (COVID‐19) pneumonia with oxygen requirements that do not require mechanical intubation, and several studies showed a reduction in disease duration. However, there is a concern about bradycardia as its side effect. We aimed to investigate the association between Remdesivir and bradycardia by integrating findings from prior studies. We queried PubMed and EMBASE in February 2023 and performed a meta‐analysis of studies investigating bradycardia in patients who did or did not receive Remdesivir. The outcome of interest was the rate of bradycardia and in‐hospital mortality. We identified eight studies involving 8993 patients, of which seven studies investigated bradycardia. Six studies were observational, one was a case–control, and one was a randomized trial. Incidence of bradycardia was 400/3480 patients (22.3%, 95% confidence interval, CI: [6.5–54.4], I2 = 99%) in the Remdesivir group and 294/5005 (9.8%, 95% CI: [2.8–29], I2 = 98.61) in the non‐Remdesivir group. The odds ratio of bradycardia was 2.11 (95% CI: [1.65–2.71], I2 = 22%, p < 0.001) for the Remdesivir group. There was no difference in mortality between the two groups. Patients who received Remdesivir for COVID‐19 were more likely to develop bradycardia. The effect of confounding factors should be considered to further clarify the possible association.

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

“…Our study, previous case reports, and studies [42] have all emphasized the importance of evaluating patient characteristics associated with bradycardia during remdesivir treatment. Gaining insights into the risk factors associated with remdesivir-induced bradycardia is crucial for making informed decisions regarding patient management and treatment approaches.…”

Safety and effectiveness of remdesivir in hospitalized patients with COVID-19 and severe renal impairment: experience at a large medical center

“…Our results showed that the risk of bradycardia in the eGFR <30 cohort was comparable to that in the eGFR ≥30 cohort. Current reports have almost exclusively compared remdesivir users with non-users, and limited studies compared the same groups as our condition [ 51 , 52 ]. Furthermore, previous studies have been inconsistent regarding whether renal function may be a risk factor for bradycardia in remdesivir recipients; while Ai et al.…”

An updated meta‐analysis of pooled incidence of remdesivir‐associated bradycardia

“…As shown in Figure 1, the updated pooled incidence of bradycardia among COVID-19 patients receiving remdesivir treatment was 32.5% (95% CI: 21.7%-45.4%, I 2 = 98.8%). The total sample size was substantially larger than that of the original analysis, 1 and the confidence intervals were narrowed, indicating improved precision of the bradycardia incidence estimate associated with remdesivir. The risk of bias was assessed using the Newcastle-Ottawa Scale (NOS) or the Cochrane Risk of Bias 2.0 (ROB 2.0) tool, which revealed that six of the included studies were classified as having a low risk of bias (i.e., NOS ≥ 7 stars) (Figure 1).…”

“…Although an association between remdesivir and bradycardia was established in the study by Ishisaka et al, 1 the wide confidence interval (i.e., 6.5%-54.4%) may indicate imprecision in the estimate of the pooled incidence. An accurate estimate of the incidence would better inform clinicians about the risks to discuss with patients and the appropriateness of cardiac monitoring.…”

“…We read with interest the article by Ishisaka et al examining the association between remdesivir treatment and bradycardia risk in COVID-19 patients. 1 The authors performed a systematic review and meta-analysis and identified eight studies with a total of 8993 patients. Their findings demonstrated that remdesivir treatment is associated with a significantly higher risk of bradycardia compared to COVID-19 patients not receiving this treatment (odds ratio 2.11, 95% confidence interval [CI]: 1.65-2.71).…”