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 4,069 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-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 4,069 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=2,057) 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, 9,700 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.
RAAS inhibitors are not associated with mortality in COVID-19 patients: findings from an observational multicenter study in Italy and a meta-analysis of 19 studies / A. Di Castelnuovo, S. Costanzo, A. Antinori, N. Berselli, L. Blandi, M. Bonaccio, R. Cauda, A. Gialluisi, G. Guaraldi, L. Menicanti, M. Mennuni, R. Mussinelli, I. My, G. Parruti, G. Patti, S. Perlini, F. Santilli, C. Signorelli, G.G. Stefanini, A. Vergori, P. Abete, W. Ageno, P. Agostoni, L. Aiello, S. Al Moghazi, R. Arboretti, F. Aucella, G. Barbieri, M. Barchitta, A. Bartoloni, P. Bonfanti, F. Cacciatore, L. Caiano, L. Carrozzi, A. Cascio, G. Castiglione, S. Cianfrone, A. Ciccullo, A. Cingolani, F. Cipollone, C. Colomba, C. Colombo, O. Cozzi, A. Crisetti, F. Crosta, G.B. Danzi, D. D'Ardes, K. de Gaetano Donati, F. Di Gennaro, G. Di Tano, G. D'Offizi, F.M. Fusco, I. Gentile, E. Graziani, G. Guarnieri, G. Larizza, A. Leone, V. Lio, M.B. Lucia, G. Maccagni, F. Madaro, S. Maitan, S. Mancarella, R. Manuele, M. Mapelli, R. Maragna, R. Marcucci, G. Maresca, S. Marongiu, C. Marotta, L. Marra, F. Mastroianni, M. Mazzitelli, A. Mengozzi, F. Menichetti, M. Meschiari, J. Milic, F. Minutolo, B. Molena, C. Mussini, M. Musso, A. Odone, M. Olivieri, A. Palimodde, E. Pasi, R. Pesavento, F. Petri, B. Pinchera, C.A. Pivato, V. Poletti, C. Ravaglia, M. Rossato, M. Rossi, A. Sabena, F. Salinaro, V. Sangiovanni, C. Sanrocco, G. Scoppettuolo, L. Scorzolini, R. Sgariglia, P.G. Simeone, E.M. Trecarichi, R. Vettor, A. Vianello, M. Vinceti, A. Virano, L. Vocciante, L. Iacoviello, R. de Caterina. - In: VASCULAR PHARMACOLOGY. - ISSN 1537-1891. - (2020). [Epub ahead of print] [10.1016/j.vph.2020.106805]
RAAS inhibitors are not associated with mortality in COVID-19 patients: findings from an observational multicenter study in Italy and a meta-analysis of 19 studies
P. Agostoni;M. Mapelli;R. Maragna;
2020
Abstract
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 4,069 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-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 4,069 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=2,057) 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, 9,700 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.
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