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.
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 / Di Castelnuovo, A.; Costanzo, S.; Antinori, A.; Berselli, N.; Blandi, L.; Bonaccio, M.; Cauda, R.; Gialluisi, A.; Guaraldi, G.; Menicanti, L.; Mennuni, M.; Mussinelli, R.; My, I.; Parruti, G.; Patti, G.; Perlini, S.; Santilli, F.; Signorelli, C.; Stefanini, G. G.; Vergori, A.; Abete, P.; Ageno, W.; Agostoni, P.; Aiello, L.; Al Moghazi, S.; Arboretti, R.; Aucella, F.; Barbieri, G.; Barchitta, M.; Bartoloni, A.; Bonfanti, P.; Cacciatore, F.; Caiano, L.; Carrozzi, L.; Cascio, A.; Castiglione, G.; Cianfrone, S.; Ciccullo, A.; Cingolani, A.; Cipollone, F.; Colomba, C.; Colombo, C.; Cozzi, O.; Crisetti, A.; Crosta, F.; Danzi, G. B.; D'Ardes, D.; de Gaetano Donati, K.; Di Gennaro, F.; Di Tano, G.; D'Offizi, G.; Fusco, F. M.; Gentile, I.; Graziani, E.; Guarnieri, G.; Larizza, G.; Leone, A.; Lio, V.; Lucia, M. B.; Maccagni, G.; Madaro, F.; Maitan, S.; Mancarella, S.; Manuele, R.; Mapelli, M.; Maragna, R.; Marcucci, R.; Maresca, G.; Marongiu, S.; Marotta, C.; Marra, L.; Mastroianni, F.; Mazzitelli, M.; Mengozzi, A.; Menichetti, F.; Meschiari, M.; Milic, J.; Minutolo, F.; Molena, B.; Mussini, C.; Musso, M.; Odone, A.; Olivieri, M.; Palimodde, A.; Pasi, E.; Pesavento, R.; Petri, F.; Pinchera, B.; Pivato, C. A.; Poletti, V.; Ravaglia, C.; Rossato, M.; Rossi, M.; Sabena, A.; Salinaro, F.; Sangiovanni, V.; Sanrocco, C.; Scoppettuolo, G.; Scorzolini, L.; Sgariglia, R.; Simeone, P. G.; Trecarichi, E. M.; Vettor, R.; Vianello, A.; Vinceti, M.; Virano, A.; Vocciante, L.; De Caterina, R.; Iacoviello, L.. - In: VASCULAR PHARMACOLOGY. - ISSN 1537-1891. - 135:(2020), p. 106805. [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
Abete P.;Cacciatore F.;Gentile I.;Pinchera B.;
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 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.| File | Dimensione | Formato | |
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