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

Vascul Pharmacol. 2020 Dec;135:106805. doi: 10.1016/j.vph.2020.106805. Epub 2020 Sep 28.


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 (ACEI) 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.

Keywords: ACE-I; ARB; Angiotensin converting enzyme inhibitors; Angiotensin receptor blockers; COVID−19; Mortality; Sartans.

Publication types

  • Multicenter Study
  • Observational Study

MeSH terms

  • Aged
  • Aged, 80 and over
  • Angiotensin Receptor Antagonists / adverse effects
  • Angiotensin Receptor Antagonists / therapeutic use*
  • Angiotensin-Converting Enzyme Inhibitors / adverse effects
  • Angiotensin-Converting Enzyme Inhibitors / therapeutic use*
  • Antihypertensive Agents / adverse effects
  • Antihypertensive Agents / therapeutic use*
  • COVID-19 / diagnosis
  • COVID-19 / mortality*
  • COVID-19 / therapy
  • Female
  • Hospital Mortality*
  • Hospitalization
  • Humans
  • Hypertension / drug therapy*
  • Hypertension / epidemiology
  • Hypertension / physiopathology
  • Incidence
  • Italy / epidemiology
  • Male
  • Meta-Analysis as Topic
  • Middle Aged
  • Renin-Angiotensin System / drug effects*
  • Risk Assessment
  • Risk Factors
  • Severity of Illness Index


  • Angiotensin Receptor Antagonists
  • Angiotensin-Converting Enzyme Inhibitors
  • Antihypertensive Agents

Associated data

  • ClinicalTrials.gov/NCT04318418