Serious bradycardia and remdesivir for coronavirus 2019 (COVID-19): a new safety concerns

Abstract

Objectives In recent clinical trials some cardiac arrhythmias were reported with use of remdesivir for COVID-19. To address this safety concern, we investigated whether use of remdesivir for COVID-19 is associated with an increased risk of bradycardia. Methods Using VigiBase®, the World Health Organization Global Individual Case Safety Reports database, we compared the cases of bradycardia reported in COVID-19 patients exposed to remdesivir with those reported in COVID-19 patients exposed to hydroxychloroquine, lopinavir/ritonavir, tocilizumab or glucocorticoids. All reports of patients with COVID-19 registered up to the 23 th of September 2020 were included. We conducted disproportionality analyses allowing the estimation of reporting odds ratios (RORs) with 95% Confident Intervals (95% CI). Results We found 302 cardiac effects including 94 bradycardia (31%) among the 2,603 reports with remdesivir prescribed in COVID-19 patients. Most of reports were serious (75, 80%) and in 16 reports (17%) evolution was fatal. Compared with hydroxychloroquine, lopinavir/ritonavir, tocilizumab or glucocorticoids, the use of remdesivir was associated with an increased risk of reporting bradycardia (ROR 1.65; 95% CI 1.23, 2.22). Consistent results were observed in other sensitivity analyses. Conclusions This post-marketing study in a real-world setting suggests that the use of remdesivir is significantly associated with an increased risk of reporting bradycardia and serious bradycardia when compared with the use of with hydroxychloroquine, lopinavir/ritonavir, tocilizumab or glucocorticoids. This result is in line with pharmacodynamic properties of the remdesivir.

Cardiac Events Potentially Associated to Remdesivir: An Analysis from the European Spontaneous Adverse Event Reporting System

“…Analyzing the time of occurrence of our cardiac AEs, our findings showed that the mean time to the onset specific for cardiac events was 3.3 days. Touafchia et al showed in their pharmacovigilance study a slightly shorter median onset of bradycardia (2.4 days; range 1–6) but results with regard to the comparison between remdesivir and hydroxychloroquine are similar to our findings [ 27 ]. Our study suggests an increased risk of reporting a cardiac event with remdesivir compared to other well-known cardiotoxic medicines used in the COVID-19 pandemic, such as azithromycin or hydroxychloroquine.…”

“…Moreover, it has also pointed out that these fatal cardiac events are to be referred to hospitalized COVID-19, a clinical condition that itself is predictive of cardiovascular risk with a fatal outcome [ 35 , 36 , 37 ]. However, our results with other real-world evidence from recently published pharmacovigilance studies, are underlying a potential safety signal for remdesivir, which has not been completely evaluated yet, even if very few cases of cardiac arrest, atrial fibrillation, arrhythmia and supraventricular tachycardia have already been observed in the pre-approval trial [ 2 , 10 , 27 ]. The risk of cardiac AEs induced by remdesivir remains largely unknown [ 38 ].…”

“…In particular, the authors found in VigiBase 302 out of 2.603 ICSRs suggestive of a cardiac adverse event related to remdesivir use. Among these cardiac reports, 94 were of bradycardia, most of these were serious and some were fatal (17%) [ 27 ].…”

Remdesivir therapy associated with Bradycardia in SARS‐CoV2

“…75% of patients with bradycardia went on to develop serious complications including death. 4 These results were very similar as seen in our study as well.…”

Remdesivir therapy causing bradycardia in COVID-19 patients: Two case reports

“…A pharmacovigilance study was conducted to assess the association of the use of remdesivir and the risk of reporting serious bradycardia. The results of the study revealed significant association between remdesivir use and the incidence of bradycardia that was mostly serious, highlighting new safety concerns [17] .…”