key: cord-0754519-e0skv0bn
authors: Tedeschi, Sara; Giannella, Maddalena; Bartoletti, Michele; Trapani, Filippo; Tadolini, Marina; Borghi, Claudio; Viale, Pierluigi
title: Clinical impact of renin-angiotensin system inhibitors on in-hospital mortality of patients with hypertension hospitalized for COVID-19
date: 2020-04-27
journal: Clin Infect Dis
DOI: 10.1093/cid/ciaa492
sha: 8b2c5f3db097ae6cd68e6df71377827b15ea8ee5
doc_id: 754519
cord_uid: e0skv0bn

nan

M a n u s c r i p t [1] .

Initial epidemiological studies have associated the presence of hypertension with a more severe disease and higher mortality rates [2, 3] . Nevertheless, it is unclear if this association is related to the pathogenesis of hypertension or to advanced age, coexisting comorbidities or antihypertensive treatment [4] . SARS-CoV-2 enter host cells after binding with angiotensin-converting enzyme 2 (ACE2); an overexpression of this enzyme has been described in hypertension, diabetes, cardiovascular diseases and in animal models of pharmacologic RAS blockade [1, 5] . Although the significance of ACE2 expression on COVID-19 pathogenesis and mortality is not specifically known, it has been hypothesized that overexpression may increase the risk of severe and fatal COVID-19 but also that RAS inhibition may mitigate clinical course, by interfering with the negative effects of angiotensin II on ACE2 downregulation in infected patients.

Consequently, it has been proposed that either the use or avoidance/withdrawal of RAS inhibitors (RASIs) could have a favourable impact on COVID-19 outcomes [1] .

To date, clinical data about the role of RASIs in COVID-19 are lacking but they are urgently needed, especially in Italy where the outbreak of COVID-19 is particularly heavy among elderly people [6] , many of whom are prescribed RASIs to treat hypertension.

To investigate whether chronic treatment with RASIs has an impact on in-hospital mortality, we selected patients with hypertension from a cohort of prospectively enrolled adults with a microbiologically confirmed diagnosis of COVID-19, hospitalized in ten Italian hospitals from February 22 nd to April 4 th 2020.

Study population consisted of 311 patients with hypertension; they were significantly older, had a higher BMI and Charlson comorbidity index with a higher prevalence of cardiovascular (CV) comorbidities, chronic obstructive pulmonary disease (COPD) and diabetes and a higher sequential organ failure assessment (SOFA) score on admission than patients without hypertension (Table) . Patients receiving antihypertensive drugs other than RASIs had a higher Charlson comorbidity index, with a higher prevalence of COPD and CV comorbidities. In the group of patients with hypertension, at multivariate Cox regression analysis adjusted for age, gender, presence of CV comorbidities and COPD, the independent predictors of in-hospital mortality were: SOFA score on admission (aHR 1.32, 95% CI 1.20-1.45; p<0.001) and age (aHR 1.05, 95% CI 1.03-1.07; p<0.001). Whereas, the chronic use of RASIs (aHR 0.97, 95% CI 0.68-1.39; p=0.88) was not associated with outcome.

Our study population consists of aged patients with multiple comorbidities, from a hospital-based cohort with a probable selection bias for sicker cases, so in-hospital mortality is very high. Nevertheless, our findings support the statements of several scientific societies that recommend patients to continue their current hypertensive medication regimen, waiting for the results of randomized controlled trials addressing the impact of RASIs on COVID-19 morbidity and mortality.

A c c e p t e d M a n u s c r i p t 

Is There an Association Between COVID-19 Mortality and the Renin-Angiotensin System-a Call for Epidemiologic Investigations

Risk Factors Associated With Acute Respiratory Distress Syndrome and Death in Patients With Coronavirus Disease

Clinical course and risk factors for mortality of adult inpatients with COVID-19 in Wuhan, China: a retrospective cohort study

COVID-19 and Angiotensin-Converting Enzyme Inhibitors and Angiotensin Receptor Blockers: What Is the Evidence? Jama

System Inhibitors in Patients with Covid-19. The New England journal of medicine

Case-Fatality Rate and Characteristics of Patients Dying in Relation to COVID-19 in Italy

A c c e p t e d M a n u s c r i p t A c c e p t e d M a n u s c r i p t