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

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