TY - JOUR
T1 - RAAS inhibitors are not associated with mortality in COVID-19 patients
T2 - Findings from an observational multicenter study in Italy and a meta-analysis of 19 studies
AU - The COvid-19 RISk and Treatments (CORIST) collaboration
AU - Di Castelnuovo, Augusto
AU - Costanzo, Simona
AU - Antinori, Andrea
AU - Berselli, Nausicaa
AU - Blandi, Lorenzo
AU - Bonaccio, Marialaura
AU - Cauda, Roberto
AU - Gialluisi, Alessandro
AU - Guaraldi, Giovanni
AU - Menicanti, Lorenzo
AU - Mennuni, Marco
AU - Mussinelli, Roberta
AU - My, Ilaria
AU - Parruti, Giustino
AU - Patti, Giuseppe
AU - Perlini, Stefano
AU - Santilli, Francesca
AU - Signorelli, Carlo
AU - Stefanini, Giulio G.
AU - Vergori, Alessandra
AU - Abete, Pasquale
AU - Ageno, Walter
AU - Agostoni, Piergiuseppe
AU - Aiello, Luca
AU - Al Moghazi, Samir
AU - Arboretti, Rosa
AU - Aucella, Filippo
AU - Barbieri, Greta
AU - Barchitta, Martina
AU - Bartoloni, Alessandro
AU - Bonfanti, Paolo
AU - Cacciatore, Francesco
AU - Caiano, Lucia
AU - Carrozzi, Laura
AU - Cascio, Antonio
AU - Castiglione, Giacomo
AU - Cianfrone, Stefania
AU - Ciccullo, Arturo
AU - Cingolani, Antonella
AU - D'Offizi, Gianpiero
AU - Fusco, Francesco Maria
AU - Mapelli, Massimo
AU - Musso, Maria
AU - Odone, Anna
AU - Olivieri, Marco
AU - Rossato, Marco
AU - Rossi, Marianna
AU - Scoppettuolo, Giancarlo
AU - Scorzolini, Laura
AU - Iacoviello, Licia
N1 - Funding Information:
We thank the 34 participating clinical Centres included in this cohort. This Article is dedicated to all patients who suffered or died, often in solitude, due to COVID-19; their tragic fate gave us moral strength to initiate and complete this research. The Authors alone are responsible for the views expressed in this article. They do not necessarily represent the views, decisions, or policies of the Institutions with which they are affiliated. None. None by any of the coauthors. Prof. Iacoviello and Di Castelnuovo had full access to all data in the study and take responsibility for the integrity of the data and the accuracy of the data analysis. Concept and design: Di Castelnuovo, Costanzo, Iacoviello, De Caterina, Acquisition, analysis, or interpretation of data: All authors. Drafting of the manuscript: Iacoviello, Di Castelnuovo, Costanzo. Critical revision of the manuscript for important intellectual content: Iacoviello, Di Castelnuovo, De Caterina, de Gaetano Donati, Guarnieri and all Authors. Statistical analysis: Di Castelnuovo, Costanzo, Arboretti, Stefanini. Administrative, technical, or material support: All Authors. Supervision: Iacoviello, Di Castelnuovo, De Caterina. Novelty and Significance? written in a style that is understood by a general audience. This section, which should be about 100 words, comprises 3 subsections under the following headings:
Publisher Copyright:
© 2020 Elsevier Inc.
Copyright:
Copyright 2020 Elsevier B.V., All rights reserved.
PY - 2020/12
Y1 - 2020/12
N2 - Objective: The hypothesis that been set forward that use of Renin Angiotensin Aldosterone System (RAAS) inhibitors is associated with COVID−19 severity. We set-up a multicenter Italian collaboration (CORIST Project, ClinicalTrials.gov ID: NCT04318418) to retrospectively investigate the relationship between RAAS inhibitors and COVID−19 in-hospital mortality. We also carried out an updated meta-analysis on the relevant studies. Methods: We analyzed 4069 unselected patients with laboratory-confirmed SARS-CoV-2 infection and hospitalized in 34 clinical centers in Italy from February 19, 2020 to May 23, 2020. The primary end-point in a time-to event analysis was in-hospital death, comparing patients who received angiotensin-converting–enzyme inhibitors (ACE[sbnd]I) or angiotensin-receptor blockers (ARB) with patients who did not. Articles for the meta-analysis were retrieved until July 13th, 2020 by searching in web-based libraries, and data were combined using the general variance-based method. Results: Out of 4069 COVID−19 patients, 13.5% and 13.3% received ACE-I or ARB, respectively. Use of neither ACE-I nor ARB was associated with mortality (multivariable hazard ratio (HR) adjusted also for COVID−19 treatments: 0.96, 95% confidence interval 0.77–1.20 and HR = 0.89, 0.67–1.19 for ACE-I and ARB, respectively). Findings were similar restricting the analysis to hypertensive (N = 2057) patients (HR = 1.00, 0.78–1.26 and HR = 0.88, 0.65–1.20) or when ACE-I or ARB were considered as a single group. Results from the meta-analysis (19 studies, 29,057 COVID−19 adult patients, 9700 with hypertension) confirmed the absence of association. Conclusions: In this observational study and meta-analysis of the literature, ACE-I or ARB use was not associated with severity or in-hospital mortality in COVID−19 patients.
AB - Objective: The hypothesis that been set forward that use of Renin Angiotensin Aldosterone System (RAAS) inhibitors is associated with COVID−19 severity. We set-up a multicenter Italian collaboration (CORIST Project, ClinicalTrials.gov ID: NCT04318418) to retrospectively investigate the relationship between RAAS inhibitors and COVID−19 in-hospital mortality. We also carried out an updated meta-analysis on the relevant studies. Methods: We analyzed 4069 unselected patients with laboratory-confirmed SARS-CoV-2 infection and hospitalized in 34 clinical centers in Italy from February 19, 2020 to May 23, 2020. The primary end-point in a time-to event analysis was in-hospital death, comparing patients who received angiotensin-converting–enzyme inhibitors (ACE[sbnd]I) or angiotensin-receptor blockers (ARB) with patients who did not. Articles for the meta-analysis were retrieved until July 13th, 2020 by searching in web-based libraries, and data were combined using the general variance-based method. Results: Out of 4069 COVID−19 patients, 13.5% and 13.3% received ACE-I or ARB, respectively. Use of neither ACE-I nor ARB was associated with mortality (multivariable hazard ratio (HR) adjusted also for COVID−19 treatments: 0.96, 95% confidence interval 0.77–1.20 and HR = 0.89, 0.67–1.19 for ACE-I and ARB, respectively). Findings were similar restricting the analysis to hypertensive (N = 2057) patients (HR = 1.00, 0.78–1.26 and HR = 0.88, 0.65–1.20) or when ACE-I or ARB were considered as a single group. Results from the meta-analysis (19 studies, 29,057 COVID−19 adult patients, 9700 with hypertension) confirmed the absence of association. Conclusions: In this observational study and meta-analysis of the literature, ACE-I or ARB use was not associated with severity or in-hospital mortality in COVID−19 patients.
KW - ACE-I
KW - Angiotensin converting enzyme inhibitors
KW - Angiotensin receptor blockers
KW - ARB
KW - COVID−19
KW - Mortality
KW - Sartans
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U2 - 10.1016/j.vph.2020.106805
DO - 10.1016/j.vph.2020.106805
M3 - Article
C2 - 32992048
AN - SCOPUS:85093963915
VL - 135
JO - Vascular Pharmacology
JF - Vascular Pharmacology
SN - 1537-1891
M1 - 106805
ER -