Association between renin–angiotensin system inhibitors and COVID-19 complications

Abstract

Aims To describe the characteristics of patients hospitalized with COVID-19 (including their long-term at-home medication use), and compare them with regard to the course of the disease. To assess the association between renin–angiotensin system inhibitors (RASIs) and disease progression and critical outcomes. Methods and results All consecutive hospitalized patients with laboratory-confirmed COVID-19 in a university hospital in Amiens (France) were included in this study. The primary composite endpoint was admission to an intensive care unit (ICU) or death before ICU admission. Univariable and multivariable logistic regression models were used to identify factors associated with the composite endpoint. Between 28 February 2020 and 30 March 2020, a total of 499 local patients tested positive for SARS-CoV-2. Of these, 231 were not hospitalized {males 33%; median [interquartile range (IQR)] age: 44 (32–54)}, and 268 were hospitalized [males 58%; median (IQR) age: 73 (61–84)]. A total of 116 patients met the primary endpoint: 47 died before ICU admission, and 69 were admitted to the ICU. Patients meeting the primary endpoint were more likely than patients not meeting the primary endpoint to have coronary heart disease and to have been taking RASIs; however, the two subsets of patients did not differ with regard to median age. After adjustment for other associated variables, the risk of meeting the composite endpoint was 1.73 times higher (odds ratio 1.73, 95% confidence interval 1.02–2.93) in patients treated at baseline with a RASI than in patients not treated with this drug class. This association was confirmed when the analysis was restricted to patients treated with antihypertensive agents. Conclusions We highlighted a potential safety signal for RASIs, the long-term use of which was independently associated with a higher risk of severe COVID-19 and a poor outcome. Due to the widespread use of this important drug class, formal proof based on clinical trials is needed to better understand the association between RASIs and complications of COVID-19.

Adverse impact of renin-angiotensin system blockade on the clinical course in hospitalized patients with severe COVID-19: a retrospective cohort study

“…We reported a negative impact of ACE-I and ARB use among hospitalized Korean patients. Liabeuf et al described the association of RAS blockade use with a higher risk of severe COVID-19 in 268 hospitalized patients, which is consistent with our results 21 . The difference of these studies compared with the previous reports is that all confounding factors such as body mass index, blood pressure, and various laboratory data were identi ed in severe hospitalized patients with COVID-19.…”

Mortality and Disease Severity Among COVID-19 Patients Receiving Renin-Angiotensin System Inhibitors: A Systematic Review and Meta-analysis

“…The characteristics of the shortlisted studies are summarized in Table 1. Among shortlisted studies, 23 studies were from China , nine studies were from Italy [64][65][66][67][68][69][70][71][72], ten studies were from the United States [83][84][85][86][87][88][89][90][91][92], four studies were from South Korea [75][76][77][78], three studies were from France [60][61][62], two studies were from Spain [79,80], one study each was from Belgium [35], Denmark [59], Hong Kong [63], Kuwait [73], Singapore [74], Turkey [81], and the United Kingdom [82]; and one study included data from 38 countries [93]. There were 24 studies that included hypertensive patients exclusively (100%) [36, 38, 39, 43-45, 47, 48, 50-52, 54, 56, 58, 66, 71, 72, 75, 78, 81, 87-89, 91].…”

“…The comparison of mortality and clinical severity outcomes between ACEI/ARB users and non-ACEI/ARB users with COVID-19 is summarized in [35,40,52,56,59,61,63,66,74,75,78,80,84,89,90,92] provided adjusted estimates for severe/critical disease with the use of an ACEI/ ARB relative to the non-use of an ACEI/ARB. , it was unclear whether the entire included cohort of patients was followed until discharge/death.…”

Severity of COVID-19 Infection in ACEI/ARB Users in Two Saudi Public Specialty Hospitals; Retrospective Cohort Study

“…Certainly, the contradictory ndings reported in different populations with regards to the severity of COVID-19 may suggest population differences at play [20][21][22][23] [47][48][49]. For example, in a study by Mehta et al in the United States, showed no signi cant association between ACEI/ARB use and mortality, while it reported potential harmful effects with ACEI/ARB use including higher hospital and ICU admissions [20].…”

“…It has been hypothesized that exposing patients to ACEI/ARB may increase the expression of ACE2 by a negative feedback mechanism, thus facilitating the binding process of coronavirus to epithelial cells of the kidney, intestine, lung, and blood vessels [15] and increasing the risk of developing severe and fatal COVID-19 disease [16][17][18]. Clinical research evidence to date has been equivocal, especially in terms of identifying differentiating factors that may mediate the ACEI/ARB and COVID-19 severity relationship [19][20][21][22][23].…”