Continuation versus discontinuation of renin-angiotensin system inhibitors in patients admitted to hospital with COVID-19: a prospective, randomised, open-label trial.


Journal

The Lancet. Respiratory medicine
ISSN: 2213-2619
Titre abrégé: Lancet Respir Med
Pays: England
ID NLM: 101605555

Informations de publication

Date de publication:
03 2021
Historique:
received: 18 10 2020
revised: 25 11 2020
accepted: 25 11 2020
pubmed: 11 1 2021
medline: 20 3 2021
entrez: 10 1 2021
Statut: ppublish

Résumé

Biological considerations suggest that renin-angiotensin system inhibitors might influence the severity of COVID-19. We aimed to evaluate whether continuing versus discontinuing renin-angiotensin system inhibitors (angiotensin-converting enzyme inhibitors or angiotensin receptor blockers) affects outcomes in patients admitted to hospital with COVID-19. The REPLACE COVID trial was a prospective, randomised, open-label trial done at 20 large referral hospitals in seven countries worldwide. Eligible participants were aged 18 years and older who were admitted to hospital with COVID-19 and were receiving a renin-angiotensin system inhibitor before admission. Individuals with contraindications to continuation or discontinuation of renin-angiotensin system inhibitor therapy were excluded. Participants were randomly assigned (1:1) to continuation or discontinuation of their renin-angiotensin system inhibitor using permuted block randomisation, with allocation concealed using a secure web-based randomisation system. The primary outcome was a global rank score in which participants were ranked across four hierarchical tiers incorporating time to death, duration of mechanical ventilation, time on renal replacement or vasopressor therapy, and multiorgan dysfunction during the hospitalisation. Primary analyses were done in the intention-to-treat population. The REPLACE COVID trial is registered with ClinicalTrials.gov, NCT04338009. Between March 31 and Aug 20, 2020, 152 participants were enrolled and randomly assigned to either continue or discontinue renin-angiotensin system inhibitor therapy (continuation group n=75; discontinuation group n=77). Mean age of participants was 62 years (SD 12), 68 (45%) were female, mean body-mass index was 33 kg/m Consistent with international society recommendations, renin-angiotensin system inhibitors can be safely continued in patients admitted to hospital with COVID-19. REPLACE COVID Investigators, REPLACE COVID Trial Social Fundraising Campaign, and FastGrants.

Sections du résumé

BACKGROUND
Biological considerations suggest that renin-angiotensin system inhibitors might influence the severity of COVID-19. We aimed to evaluate whether continuing versus discontinuing renin-angiotensin system inhibitors (angiotensin-converting enzyme inhibitors or angiotensin receptor blockers) affects outcomes in patients admitted to hospital with COVID-19.
METHODS
The REPLACE COVID trial was a prospective, randomised, open-label trial done at 20 large referral hospitals in seven countries worldwide. Eligible participants were aged 18 years and older who were admitted to hospital with COVID-19 and were receiving a renin-angiotensin system inhibitor before admission. Individuals with contraindications to continuation or discontinuation of renin-angiotensin system inhibitor therapy were excluded. Participants were randomly assigned (1:1) to continuation or discontinuation of their renin-angiotensin system inhibitor using permuted block randomisation, with allocation concealed using a secure web-based randomisation system. The primary outcome was a global rank score in which participants were ranked across four hierarchical tiers incorporating time to death, duration of mechanical ventilation, time on renal replacement or vasopressor therapy, and multiorgan dysfunction during the hospitalisation. Primary analyses were done in the intention-to-treat population. The REPLACE COVID trial is registered with ClinicalTrials.gov, NCT04338009.
FINDINGS
Between March 31 and Aug 20, 2020, 152 participants were enrolled and randomly assigned to either continue or discontinue renin-angiotensin system inhibitor therapy (continuation group n=75; discontinuation group n=77). Mean age of participants was 62 years (SD 12), 68 (45%) were female, mean body-mass index was 33 kg/m
INTERPRETATION
Consistent with international society recommendations, renin-angiotensin system inhibitors can be safely continued in patients admitted to hospital with COVID-19.
FUNDING
REPLACE COVID Investigators, REPLACE COVID Trial Social Fundraising Campaign, and FastGrants.

Identifiants

pubmed: 33422263
pii: S2213-2600(20)30558-0
doi: 10.1016/S2213-2600(20)30558-0
pmc: PMC7832152
pii:
doi:

Substances chimiques

Angiotensin Receptor Antagonists 0
Angiotensin-Converting Enzyme Inhibitors 0

Banques de données

ClinicalTrials.gov
['NCT04338009']

Types de publication

Journal Article Multicenter Study Randomized Controlled Trial Research Support, N.I.H., Extramural Research Support, Non-U.S. Gov't

Langues

eng

Sous-ensembles de citation

IM

Pagination

275-284

Subventions

Organisme : NHLBI NIH HHS
ID : K23 HL133843
Pays : United States
Organisme : NIDDK NIH HHS
ID : P30 DK092926
Pays : United States
Organisme : NHLBI NIH HHS
ID : R03 HL146874
Pays : United States
Organisme : NHLBI NIH HHS
ID : R01 HL104106
Pays : United States
Organisme : NHLBI NIH HHS
ID : R61 HL146390
Pays : United States
Organisme : NHLBI NIH HHS
ID : R01 HL121510
Pays : United States
Organisme : NHLBI NIH HHS
ID : R56 HL136730
Pays : United States
Organisme : NIA NIH HHS
ID : R01 AG058969
Pays : United States
Organisme : NHLBI NIH HHS
ID : P01 HL094307
Pays : United States
Organisme : NIDDK NIH HHS
ID : T32 DK007785
Pays : United States
Organisme : NHLBI NIH HHS
ID : T32 HL007891
Pays : United States
Organisme : NHLBI NIH HHS
ID : R01 HL153646
Pays : United States

Commentaires et corrections

Type : CommentIn
Type : CommentIn

Informations de copyright

Copyright © 2021 Elsevier Ltd. All rights reserved.

Auteurs

Jordana B Cohen (JB)

Renal-Electrolyte and Hypertension Division, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA; Department of Biostatistics, Epidemiology, and Informatics, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA.

Thomas C Hanff (TC)

Department of Biostatistics, Epidemiology, and Informatics, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA; Division of Cardiovascular Medicine, Hospital of the University of Pennsylvania and Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA.

Preethi William (P)

Division of Cardiology, University of Arizona, Tucson, AZ, USA.

Nancy Sweitzer (N)

Division of Cardiology, University of Arizona, Tucson, AZ, USA.

Nelson R Rosado-Santander (NR)

Department of Medicine, Hospital Nacional Carlos Alberto Seguín Escobedo, Arequipa, Peru.

Carola Medina (C)

Department of Nephrology, Hospital Nacional Edgardo Rebagliati Martins, Lima, Peru.

Juan E Rodriguez-Mori (JE)

Department of Nephrology, Hospital Nacional Alberto Sabogal Sologuren, Lima, Peru.

Nicolás Renna (N)

Hypertension Unit, Department of Pathology, Hospital Español de Mendoza, National University of Cuyo, IMBECU-CONICET, Mendoza, Argentina.

Tara I Chang (TI)

Division of Nephrology, Stanford University School of Medicine, Stanford, CA, USA.

Vicente Corrales-Medina (V)

Division of Infectious Diseases, University of Ottawa and The Ottawa Hospital Research Institute, Ottawa, ON, Canada.

Jaime F Andrade-Villanueva (JF)

Unidad de VIH, Hospital Civil de Guadalajara and Universidad de Guadalajara, Guadalajara, Mexico.

Alejandro Barbagelata (A)

Universidad Católica de Buenos Aires, Buenos Aires, Argentina; Division of Cardiology, Department of Medicine, Duke University School of Medicine, Durham, NC, USA.

Roberto Cristodulo-Cortez (R)

Departamento de Medicina Interna, Hospital Obrero number 3 Caja Nacional de Salud, Santa Cruz de la Sierra, Bolivia.

Omar A Díaz-Cucho (OA)

Departamento de Medicina, Hospital Alberto Barton Thompson, Callao, Peru.

Jonas Spaak (J)

Department of Clinical Sciences, Danderyd University Hospital, Karolinska Institutet, Stockholm, Sweden.

Carlos E Alfonso (CE)

Division of Cardiology, University of Miami Miller School of Medicine, Miami, FL, USA.

Renzo Valdivia-Vega (R)

Department of Nephrology, Hospital Nacional Edgardo Rebagliati Martins, Lima, Peru.

Mirko Villavicencio-Carranza (M)

Department of Nephrology, Hospital Nacional Edgardo Rebagliati Martins, Lima, Peru.

Ricardo J Ayala-García (RJ)

Departamento de Emergencia, Hospital Nacional Edgardo Rebagliati Martins, Lima, Peru.

Carlos A Castro-Callirgos (CA)

Department of Nephrology, Hospital Nacional Alberto Sabogal Sologuren, Lima, Peru.

Luz A González-Hernández (LA)

Unidad de VIH, Hospital Civil de Guadalajara and Universidad de Guadalajara, Guadalajara, Mexico.

Eduardo F Bernales-Salas (EF)

Department of Medicine, Hospital Nacional Carlos Alberto Seguín Escobedo, Arequipa, Peru.

Johanna C Coacalla-Guerra (JC)

Department of Medicine, Hospital Nacional Carlos Alberto Seguín Escobedo, Arequipa, Peru.

Cynthia D Salinas-Herrera (CD)

Department of Medicine, Hospital Nacional Carlos Alberto Seguín Escobedo, Arequipa, Peru.

Liliana Nicolosi (L)

Division of Cardiology, Department of Medicine, Hospital Español, Buenos Aires, Argentina.

Mauro Basconcel (M)

Division of Cardiology, Department of Medicine, Hospital Español, Buenos Aires, Argentina.

James B Byrd (JB)

Division of Cardiovascular Medicine, University of Michigan Medical School, Ann Arbor, MI, USA.

Tiffany Sharkoski (T)

Division of Cardiovascular Medicine, Hospital of the University of Pennsylvania and Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA.

Luis E Bendezú-Huasasquiche (LE)

Departamento de Medicina, Hospital Alberto Barton Thompson, Callao, Peru.

Jesse Chittams (J)

Department of Biostatistics, Epidemiology, and Informatics, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA.

Daniel L Edmonston (DL)

Division of Nephrology, Department of Medicine, Duke University School of Medicine, Durham, NC, USA.

Charles R Vasquez (CR)

Department of Biostatistics, Epidemiology, and Informatics, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA; Department of Surgery, Hospital of the University of Pennsylvania and Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA.

Julio A Chirinos (JA)

Division of Cardiovascular Medicine, Hospital of the University of Pennsylvania and Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA. Electronic address: julio.chirinos@uphs.upenn.edu.

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