Cardiovascular events and safety outcomes associated with remdesivir using a World Health Organization international pharmacovigilance database
Se Yong Jung
(1)
,
Min Seo Kim
(2, 3)
,
Han Li
(4)
,
Keum Hwa Lee
(1)
,
Ai Koyanagi
(5, 6, 7)
,
Marco Solmi
(8, 9)
,
Andreas Kronbichler
(10)
,
Elena Dragioti
(11)
,
Kalthoum Tizaoui
(12)
,
Sarah Cargnin
(13)
,
Salvatore Terrazzino
(13)
,
Sung Hwi Hong
(1)
,
Ramy Abou Ghayda
(14)
,
Nam Kyun Kim
(15, 1)
,
Seo Kyoung Chung
(16)
,
Louis Jacob
(5, 17)
,
Joe‐elie Salem
(18, 19)
,
Dong Keon Yon
(20)
,
Seung Won Lee
(21)
,
Karel Kostev
(22)
,
Ah Young Kim
(1)
,
Jo Won Jung
(1)
,
Jae Young Choi
(1)
,
Jin Soo Shin
(23)
,
Soon‐jung Park
,
Seong Woo Choi
(20)
,
Kiwon Ban
(24)
,
Sung‐hwan Moon
,
Yun Young Go
(24)
,
Jae Il Shin
(1)
,
Lee Smith
(25)
1
Yonsei University
2 Korea University [Seoul]
3 SKKU - Sungkyunkwan University [Suwon]
4 The University of Florida College of Medicine
5 UB - Universitat de Barcelona
6 ICREA - Institució Catalana de Recerca i Estudis Avançats = Catalan Institution for Research and Advanced Studies
7 ISC - Instituto de Salud Carlos III [Madrid]
8 University of Ottawa [Ottawa]
9 The Ottawa Hospital
10 IMU - Innsbruck Medical University = Medizinische Universität Innsbruck
11 LIU - Linköping University
12 University of Tunis - Faculty of Sciences of Tunis
13 UPO - Università degli Studi del Piemonte Orientale - Amedeo Avogadro
14 Case Western Reserve University [Cleveland]
15 Emory University [Atlanta, GA]
16 EWHA - EWHA Womans University
17 UVSQ - Université de Versailles Saint-Quentin-en-Yvelines
18 CIC Paris-Est - Centre d'investigation clinique Paris Est [CHU Pitié Salpêtrière]
19 CHU Pitié-Salpêtrière [AP-HP]
20 SNUCM - Seoul National University College of Medicine [Séoul, Corée du Sud]
21 College of Convergence Software (Myongji University)
22 Philipps Universität Marburg = Philipps University of Marburg
23 KRICT - Korean Research Institute of Chemical Technology
24 CUHK - City University of Hong Kong [Hong Kong]
25 ARU - Anglia Ruskin University
2 Korea University [Seoul]
3 SKKU - Sungkyunkwan University [Suwon]
4 The University of Florida College of Medicine
5 UB - Universitat de Barcelona
6 ICREA - Institució Catalana de Recerca i Estudis Avançats = Catalan Institution for Research and Advanced Studies
7 ISC - Instituto de Salud Carlos III [Madrid]
8 University of Ottawa [Ottawa]
9 The Ottawa Hospital
10 IMU - Innsbruck Medical University = Medizinische Universität Innsbruck
11 LIU - Linköping University
12 University of Tunis - Faculty of Sciences of Tunis
13 UPO - Università degli Studi del Piemonte Orientale - Amedeo Avogadro
14 Case Western Reserve University [Cleveland]
15 Emory University [Atlanta, GA]
16 EWHA - EWHA Womans University
17 UVSQ - Université de Versailles Saint-Quentin-en-Yvelines
18 CIC Paris-Est - Centre d'investigation clinique Paris Est [CHU Pitié Salpêtrière]
19 CHU Pitié-Salpêtrière [AP-HP]
20 SNUCM - Seoul National University College of Medicine [Séoul, Corée du Sud]
21 College of Convergence Software (Myongji University)
22 Philipps Universität Marburg = Philipps University of Marburg
23 KRICT - Korean Research Institute of Chemical Technology
24 CUHK - City University of Hong Kong [Hong Kong]
25 ARU - Anglia Ruskin University
Andreas Kronbichler
- Fonction : Auteur
- PersonId : 802232
- ORCID : 0000-0002-2945-2946
Salvatore Terrazzino
- Fonction : Auteur
- PersonId : 813652
- ORCID : 0000-0002-4909-1121
Louis Jacob
- Fonction : Auteur
- PersonId : 801210
- ORCID : 0000-0003-1071-1239
Joe‐elie Salem
- Fonction : Auteur
- PersonId : 777251
- IdHAL : joe-elie-salem
- ORCID : 0000-0002-0331-3307
- IdRef : 160947227
Dong Keon Yon
- Fonction : Auteur
- PersonId : 813653
- ORCID : 0000-0003-1628-9948
Seung Won Lee
- Fonction : Auteur
- PersonId : 813654
- ORCID : 0000-0001-5632-5208
Soon‐jung Park
- Fonction : Auteur
Sung‐hwan Moon
- Fonction : Auteur
Résumé
On October 2020, the US Food and Drug Administration (FDA) approved remdesivir as the first drug for the treatment of coronavirus disease 2019 (COVID-19), increasing remdesivir prescriptions worldwide. However, potential cardiovascular (CV) toxicities associated with remdesivir remain unknown. We aimed to characterize the CV adverse drug reactions (ADRs) associated with remdesivir using VigiBase, an individual case safety report database of the World Health Organization (WHO). Disproportionality analyses of CV-ADRs associated with remdesivir were performed using reported odds ratios and information components. We conducted in vitro experiments using cardiomyocytes derived from human pluripotent stem cell cardiomyocytes (hPSC-CMs) to confirm cardiotoxicity of remdesivir. To distinguish drug-induced CV-ADRs from COVID-19 effects, we restricted analyses to patients with COVID-19 and found that, after adjusting for multiple confounders, cardiac arrest (adjusted odds ratio [aOR]: 1.88, 95% confidence interval [CI]: 1.08-3.29), bradycardia (aOR: 2.09, 95% CI: 1.24-3.53), and hypotension (aOR: 1.67, 95% CI: 1.03-2.73) were associated with remdesivir. In vitro data demonstrated that remdesivir reduced the cell viability of hPSC-CMs in time- and dose-dependent manners. Physicians should be aware of potential CV consequences following remdesivir use and implement adequate CV monitoring to maintain a tolerable safety margin.
Trial registration: ClinicalTrials.gov NCT04314817.