Download PDF
Drug Res (Stuttg) 2024; 74(06): 290-295
DOI: 10.1055/a-2332-3253
Original Article

Remdesivir-Related Cardiac Adverse Effects in COVID-19 Patients: A Case-Control Study

Fatemah Abedipour
1   Department of Infectious Disease, School of Medicine, Zahedan University of Medical Sciences, Zahedan, Iran
2   Infectious Diseases and Tropical Medicine Research Center, Research Institute of Cellular and Molecular Sciences in Infectious Diseases, Zahedan University of Medical Sciences, Zahedan, Iran
,
Hossein Hadavand Mirzaei
1   Department of Infectious Disease, School of Medicine, Zahedan University of Medical Sciences, Zahedan, Iran
,
Hossein Ansari
3   Health Promotion Research Center, Zahedan University of Medical Sciences, Zahedan, Iran
,
Neda Ehsanzadeh
4   Department of Cardiology, School of Medicine, Zahedan University of Medical Sciences, Zahedan, Iran
,
Amin Rashki
5   Pharmacology Research Center, Zahedan University of Medical Sciences, Zahedan, Iran
,
Mohammad Mahdi Vahedi
5   Pharmacology Research Center, Zahedan University of Medical Sciences, Zahedan, Iran
6   Department of Pharmacology, School of Medicine, Zahedan University of Medical Sciences, Zahedan, Iran
,
Asma Rashki 
5   Pharmacology Research Center, Zahedan University of Medical Sciences, Zahedan, Iran
6   Department of Pharmacology, School of Medicine, Zahedan University of Medical Sciences, Zahedan, Iran
› Author Affiliations
› Further Information
Also available at
    Permissions and Reprints

Abstract

Background There have been reports of serious side effects of Remdesivir, including cardiovascular complications. The present study aimed to determine the adverse cardiovascular effects of Remdesivir and the factors affecting them in COVID-19 patients.

Methods The patients were classified into two groups: those receiving Remdesivir without cardiac complications and those receiving Remdesivir with cardiovascular complications. After reviewing the patientʼs medical records, the relationship of some factors with the incidence of adverse cardiovascular effects was measured.

Results Chi-square test showed that the distribution of complications in men was significantly higher than in women (P=0.001). The independent t-test revealed that the mean age in the group with complications was significantly higher than the group without complications (P=0.013). Fisherʼs exact test demonstrated a significant relationship between smoking and cardiovascular complications (P=0.05). According to the Mann-Whitney test, a significant difference was found in the mean changes of Bilirubin (P=0.02) and ALKP (P=0.01) before and after treatment in the groups with and without heart complications.

Conclusion Our findings indicated that most of the COVID-19 patients suffered from sinus bradycardia, and the distribution of complications was more pronounced in men than in women. The mean age in the group with complications was higher than the group without complications. Smoking was found to be associated with the occurrence of cardiovascular complications and the mean changes of Bilirubin and ALKP before and after treatment were significantly different in the groups with and without cardiovascular complications.

Keywords

remdesivir - cardiovascular system - side effects - COVID-19


Publication History

Received: 25 December 2023

Accepted: 22 May 2024

Article published online:
05 July 2024

© 2024. Thieme. All rights reserved.

Georg Thieme Verlag KG
Rüdigerstraße 14, 70469 Stuttgart, Germany

 

  • References

  • 1 Jorgensen SCJ, Kebriaei R, Dresser LD. Remdesivir: Review of Pharmacology, Pre-clinical Data, and Emerging Clinical Experience for COVID-19. Pharmacotherapy. 2020; 40: 659-671
    CrossrefPubMedSearch in Google Scholar
  • 2 Amirian ES, Levy JK. Current knowledge about the antivirals remdesivir (GS-5734) and GS-441524 as therapeutic options for coronaviruses. One Health 2020; 9: 100-128
    CrossrefPubMedSearch in Google Scholar
  • 3 Gordon CJ, Tchesnokov EP, Feng JY. et al. The antiviral compound remdesivir potently inhibits RNA-dependent RNA polymerase from Middle East respiratory syndrome coronavirus. J Biol Chem 2020; 295: 4773-4779
    CrossrefPubMedSearch in Google Scholar
  • 4 Malin JJ, Suárez I, Priesner V. et al. Remdesivir against COVID-19 and Other Viral Diseases. Clin Microbiol Rev 2020; 34: e00162-20
    CrossrefPubMedSearch in Google Scholar
  • 5 Wang M, Cao R, Zhang L. et al. Remdesivir and chloroquine effectively inhibit the recently emerged novel coronavirus (2019-nCoV) in vitro. Cell Res 2020; 30: 269-271
    CrossrefPubMedSearch in Google Scholar
  • 6 Pruijssers AJ, George AS, Schäfer A. et al. Remdesivir Inhibits SARS-CoV-2 in Human Lung Cells and Chimeric SARS-CoV Expressing the SARS-CoV-2 RNA Polymerase in Mice. Cell Rep 2020; 32: 107940
    CrossrefPubMedSearch in Google Scholar
  • 7 Spinner CD, Gottlieb RL, Criner GJ. et al. Effect of Remdesivir vs Standard Care on Clinical Status at 11 Days in Patients With Moderate COVID-19: A Randomized Clinical Trial. JAMA. 2020; 324: 1048-1057
    CrossrefPubMedSearch in Google Scholar
  • 8 Beigel JH, Tomashek KM, Dodd LE. et al. Remdesivir for the Treatment of Covid-19 - Final Report. N Engl J Med 2020; 383: 1813-1826
    CrossrefPubMedSearch in Google Scholar
  • 9 Pan H, Peto R, Henao-Restrepo AM. et al. Repurposed Antiviral Drugs for Covid-19 - Interim WHO Solidarity Trial Results. N Engl J Med 2021; 384: 497-511
    CrossrefPubMedSearch in Google Scholar
  • 10 Goldman JD, Lye DCB, Hui DS. et al. Remdesivir for 5 or 10 Days in Patients with Severe Covid-19. N Engl J Med 2020; 383: 1827-1837
    CrossrefPubMedSearch in Google Scholar
  • 11 Grein J, Ohmagari N, Shin D. et al. Compassionate Use of Remdesivir for Patients with Severe Covid-19. N Engl J Med 2020; 382: 2327-2336
    CrossrefPubMedSearch in Google Scholar
  • 12 Gottlieb RL, Vaca CE, Paredes R. et al. Early Remdesivir to Prevent Progression to Severe Covid-19 in Outpatients. N Engl J Med 2022; 386: 305-315
    CrossrefPubMedSearch in Google Scholar
  • 13 Hsu J. Covid-19: What now for remdesivir?. BMJ 2020; 371: m4457
    CrossrefPubMedSearch in Google Scholar
  • 14 Brunetti ND, Poliseno M, Bottalico IF. et al. Safety and heart rate changes in Covid-19 patients treated with Remdesivir. Int J Infect Dis 2021; 112: 254-257
    CrossrefPubMedSearch in Google Scholar
  • 15 Gupta AK, Parker BM, Priyadarshi V. et al. Cardiac adverse events with remdesivir in COVID-19 infection. Cureus 2020; 12: e11132
    PubMedSearch in Google Scholar
  • 16 Mulangu S, Dodd LE, Davey RT. et al. A randomized, controlled trial of Ebola virus disease therapeutics. N Engl J Med 2019; 381: 2293-2303
    CrossrefPubMedSearch in Google Scholar
  • 17 Nabati M, Parsaee H. Potential Cardiotoxic Effects of Remdesivir on Cardiovascular System: A Literature Review. Cardiovasc Toxicol 2022; 22: 268-272
    CrossrefPubMedSearch in Google Scholar
  • 18 Pallotto C, Suardi LR, Gabbuti A. et al. Potential remdesivir-related transient bradycardia in patients with coronavirus disease 2019 (COVID-19). J Med Virol 2021; 93: 2631-2634
    CrossrefPubMedSearch in Google Scholar
  • 19 Gubitosa JC, Kakar P, Gerula C. et al. Marked sinus bradycardia associated with remdesivir in COVID-19: a case and literature review. JACC Case Rep 2020; 2: 2260-2264
    CrossrefPubMedSearch in Google Scholar
  • 20 Attena E, Albani S, Maraolo AE. et al. Remdesivir-induced bradycardia in COVID-19: a single center prospective study. Circ Arrhythm Electrophysiol 2021; 14: e009811
    CrossrefPubMedSearch in Google Scholar
  • 21 Touafchia A, Bagheri H, Carrié D. et al. Serious bradycardia and remdesivir for coronavirus 2019 (COVID-19): a new safety concerns. Clin Microbiol Infect 2021; 27: 791.e5-8
    CrossrefPubMedSearch in Google Scholar
  • 22 Kanagala SG, Dholiya H, Jhajj P. et al. Remdesivir-Induced Bradycardia. South Med J 2023; 116: 317-320
    CrossrefPubMedSearch in Google Scholar
  • 23 Choi SW, Shin JS, Park SJ. et al. Antiviral activity and safety of remdesivir against SARS-CoV-2 infection in human pluripotent stem cell-derived cardiomyocytes. Antiviral Res 2020; 184: 104955
    CrossrefPubMedSearch in Google Scholar
  • 24 Pelleg A, Belhassen B. The mechanism of the negative chronotropic and dromotropic actions of adenosine 5ʼ-triphosphate in the heart: an update. J Cardiovasc Pharmacol 2010; 56: 106-109
    CrossrefPubMedSearch in Google Scholar
  • 25 Onakpoya IJ. Rare adverse events in clinical trials: understanding the rule of three. BMJ Evid Based Med 2018; 23: 6
    CrossrefPubMedSearch in Google Scholar
  • 26 Rafaniello C, Ferrajolo C, Sullo MG. et al. Cardiac Events Potentially Associated to Remdesivir: An Analysis from the European Spontaneous Adverse Event Reporting System. Pharmaceuticals (Basel) 2021; 14: 611
    CrossrefPubMedSearch in Google Scholar
  • 27 Ogawa A, Ohira S, Kato Y. et al. Activation of the urotensin-II receptor by remdesivir induces cardiomyocyte dysfunction. Commun Biol 2023; 6: 511
    CrossrefPubMedSearch in Google Scholar
  • 28 Alsowaida YS, Shehadeh F, Kalligeros M. et al. Incidence and potential risk factors for remdesivir-associated bradycardia in hospitalized patients with COVID-19: A retrospective cohort study. Front Pharmacol 2023; 14: 1106044
    CrossrefPubMedSearch in Google Scholar
  • 29 Jung SY, Kim MS, Li H. et al. Cardiovascular events and safety outcomes associated with remdesivir using a World Health Organization international pharmacovigilance database. Clin Transl Sci 2022; 15: 501-513
    CrossrefPubMedSearch in Google Scholar
  • 30 Strait JB, Lakatta EG. Aging-associated cardiovascular changes and their relationship to heart failure. Heart Fail Clin 2012; 8: 143-164
    CrossrefPubMedSearch in Google Scholar
  • 31 Kim MM, Steffensen I, Miguel RTD. et al. Study title: A systematic review of RCTs to examine the risk of adverse cardiovascular events with nicotine use. Front Cardiovasc Med 2023; 10: 1111673
    CrossrefPubMedSearch in Google Scholar
  • 32 Haarhaus M, Brandenburg V, Kalantar-Zadeh K. et al. Alkaline phosphatase: a novel treatment target for cardiovascular disease in CKD. Nat Rev Nephrol 2017; 13: 429-442
    CrossrefPubMedSearch in Google Scholar
  • 33 Li J-W, Xu C, Fan Y. et al. Can serum levels of alkaline phosphatase and phosphate predict cardiovascular diseases and total mortality in individuals with preserved renal function? A systemic review and meta-analysis. PLoS One 2014; 9: e102276
    CrossrefPubMedSearch in Google Scholar
  • 34 Wu C, Song W, Xu Y. et al. The Nonlinear Relationship Between Total Bilirubin and Coronary Heart Disease: A Dose-Response Meta-Analysis. Front Cardiovasc Med 2021; 8: 761520
    PubMedSearch in Google Scholar
  • 35 Horsfall LJ, Nazareth I, Petersen I. Cardiovascular events as a function of serum bilirubin levels in a large, statin-treated cohort. Circulation. 2012; 126: 2556-2564
    CrossrefPubMedSearch in Google Scholar
  • 36 Arya S, Kumar P, Tiwari B. et al. What Every Intensivist should Know about Impairment of Cardiac Function and Arrhythmias in Liver Disease Patients: A Review. Indian J Crit Care Med 2020; 24: 1251-1255
    CrossrefPubMedSearch in Google Scholar
  • 37 Adamson C, Butt JH, Rouleau J. et al. Alkaline phosphatase and bilirubin combined are a powerful predictor of outcome in patients with heart failure and reduced ejection fraction: an analysis of the ATMOSPHERE and PARADIGM-HF trials. European Heart Journal 2022; 43: 544-871
    CrossrefPubMedSearch in Google Scholar