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

The hypothesis that been set forward that use of Renin Angiotensin Aldosterone System (RAAS) inhibitors is associated with COVID−19 severity. We setup 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 (ACEeI) 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.

First and second waves of coronavirus disease-19: A comparative study in hospitalized patients in Reus, Spain

“…The present study did not find any differences between the frequency of concomitant diseases in the two waves, similar findings to those of our preliminary study [ 11 ]. In this respect, we differ from a previous study conducted in Japan that has reported a lower incidence of cardiovascular and cerebrovascular diseases [ 3 ], and also from a multicenter study in Italy [ 28 , 29 ] that identified impaired renal function, but not obesity, cardiovascular disease or cancer, as the major predictors of in-hospital death.…”

A comprehensive guide to the pharmacologic regulation of angiotensin converting enzyme 2 (ACE2), the SARS-CoV-2 entry receptor

“…In recent months, several clinical studies have reported that the use of ARBs and ACE-Inhs. does not affect disease progression and mortality rates in COVID-19 patients ( Anzola et al, 2020 ; Bae et al, 2020 ; Braude et al, 2020 ; Cordeanu et al, 2020 ; H. Cui et al, 2020 ; Di Castelnuovo et al, 2020 ; Gormez et al, 2020 ; Hippisley-Cox et al, 2020 ; Kalra et al, 2020 ; Khan et al, 2020 , Kim et al, 2020 ; Kocayigit et al, 2020 ; Lafaurie et al, 2020 ; J. Lee et al, 2020 ; Sardu et al, 2020 ; Soleimani et al, 2020 , Taher et al, 2020 ; Trifirò et al, 2020 , Wang et al, 2020 ). Altogether, these results indicate that the use of ACE-Inhs.…”

Clinical and radiological findings of adult hospitalized patients with community-acquired pneumonia from SARS-CoV-2 and endemic human coronaviruses

“…Second, in the SARS-CoV-2 group, several patients with mild symptoms were hospitalized at the early stage of the outbreak for isolation purposes. Compared to studies that included a large study population, our study had a lower mortality rate of SARS-CoV-2 infection [ 22 , 23 ]. In the case of endemic HCoVs, only patients who needed inpatient treatment were selected, so there may be differences in severity between the two groups.…”