Cardiac adverse events associated with remdesivir in COVID-19 patients: a systematic review and meta-analysis of randomised controlled trials

Abstract

Objectives: To evaluate whether remdesivir is associated with cardiac adverse events (CAEs), addressing concerns raised by basic experiments, clinical case reports and observational studies.

Design: Systematic review and meta-analysis.

Data sources: MEDLINE and Embase, searched from January 2020 to December 2023.

Study selection: Randomised controlled trials (RCTs) comparing remdesivir with placebo or standard care in patients with COVID-19, with a primary focus on cardiac safety.

Eligibility criteria for selecting studies: We included RCTs that evaluated the safety of remdesivir in patients with COVID-19 . Eligible studies were those that compared remdesivir with placebo or standard care in adult patientsCOVID-19 . Inclusion criteria emphasised safety outcomes, particularly CAEs, as primary endpoints.

Data extraction and synthesis: Two reviewers independently extracted data. Reporting followed the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA)-Harms guidelines. Risk of bias (RoB) was assessed using the Cochrane Collaboration tool. A random-effects model was used for data synthesis. The Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach was applied to assess the certainty of evidence. The primary outcome was the incidence of any CAEs, defined as a composite of all reported cardiac-related harms. Secondary outcomes included specific CAEs such as arrhythmias, heart failure and myocardial disorders.

Results: We identified 1698 studies, of which seven RCTs met the inclusion criteria, comprising a total of 4566 participants. The RoB was assessed across multiple domains, with four RCTs showing low risk and three showing moderate risk in specific areas. Pooled analysis revealed no significant association between remdesivir use and CAEs (RR=0.84, 95% CI: 0.68 to 1.04, p=0.118). Subgroup analyses showed consistent findings across different patient demographics and comorbidities. GRADE assessment indicated moderate certainty for overall CAEs, low certainty for arrhythmias and heart failure (due to imprecision and study-level bias), and very low certainty for myocardial disorders (due to small sample size and indirectness).

Conclusions: Contrary to preliminary concerns and case reports, our meta-analysis found no evidence of a statistically significant association between remdesivir and CAEs among patients with COVID-19 . These findings provide reassurance to clinicians regarding the safety profile of remdesivir in this patient population, supporting its use as an antiviral therapy in the treatment of COVID-19. Further research is warranted to validate these findings and to clarify whether remdesivir may have a neutral or potentially protective effect on cardiac outcomes.

Prospero registration number: CRD42022383647.

Keywords: Adverse events; COVID-19; Meta-Analysis; SARS-CoV-2 Infection; Safety; Systematic Review.

Figure 1. Preferred Reporting Items for Systematic Reviews and Meta-Analyses flow diagram of study selection. Flow diagram illustrating the identification, screening, eligibility assessment, and final inclusion of studies in the systematic review and meta-analysis. CAE, cardiac adverse events.

Figure 2. Forest plot of cardiac adverse events (CAEs) in patients treated with remdesivir vs standard care. Pooled risk ratios (RRs) with 95% CIs are shown for each of the seven included randomised controlled trials, along with the total number of events and participants in each group. The diamond represents the overall pooled RR calculated using a random-effects model. No statistically significant difference was observed between groups.

Figure 3. Comparison of female (A) and male (B) patients having cardiac adverse events based on whether they were treated with remdesivir or standard of care. Risk ratios and 95% confidence intervals are shown for each study. CAE, cardiac adverse events.