scholarly journals Impact of Chronic RAAS Use in Elderly COVID-19 Patients: A Retrospective Analysis

2021 ◽  
Vol 10 (14) ◽  
pp. 3147
Author(s):  
João Oliveira ◽  
Joana Gameiro ◽  
João Bernardo ◽  
Filipe Marques ◽  
Cláudia Costa ◽  
...  

Corona Virus Disease-19 (COVID-19) recently emerged as a global pandemic. Advanced age is the most important risk factor for increased virus susceptibility and worse outcomes. Many older adults are currently treated with renin–angiotensin–aldosterone system (RAAS) inhibitors and there is concern that these medications might increase the risk of mortality by COVID-19. This is a retrospective cohort of 346 patients older than 65 years with COVID-19, at the Department of Medicine of the Centro Hospitalar Universitário Lisboa Norte, in Portugal, hospitalized between March 2020 and August 2020. Mean age was 80.9 ± 8.7 years old. Most patients had arterial hypertension (n = 279, 80.6%), almost half (n = 161, 46.5%) had cardiovascular disease and approximately one-third of patients had heart failure (n = 127, 36.7%) or diabetes Mellitus (n = 113, 32.7%). Ninety-eight patients (28.3%) had chronic kidney disease and almost half of the patients (49.4%) were chronically under renin–angiotensin–aldosterone system (RAAS) inhibitors. Twenty percent of patients died during hospitalization. In a multivariate analysis, older age (OR 1.11, 95% CI 1.04, 1.18, p = 0.002), absence of baseline medication with RAAS inhibitors (OR 0.27, 95% CI 0.10, 0.75, p = 0.011), higher serum ferritin (OR 1.00, 95% CI 1.00, 1.00, p = 0.003) and higher lactate levels (OR 1.08, 95% CI 1.02, 1.14, p = 0.006) were independent predictors of mortality. Older age, higher serum ferritin and lactate levels at admission were found to be independent predictors of mortality and might act as early predictors of worsening disease in clinical practice. Chronic treatment with RAAS inhibitors appeared to be protective, supporting guidelines in not discontinuing such drugs.

Author(s):  
Davide Ventura ◽  
Amy L Carr ◽  
R Duane Davis ◽  
Scott Silvestry ◽  
Linda Bogar ◽  
...  

Abstract It has been established SARS-CoV-2 uses angiotensin-converting enzyme 2 (ACE2), a membrane-bound regulatory peptide, for host cell entry. Renin-angiotensin-aldosterone system (RAAS) inhibitors have been reported to increase ACE2 in type 2 pneumocytes pulmonary tissue. Controversy exists for the continuation of ACE inhibitors, angiotensin II receptor blockers (ARBs), and mineralocorticoid receptor antagonists (MRAs) in the current pandemic. ACE2 serves as regulatory enzyme in maintaining homeostasis between proinflammatory Angiotensin II and anti-inflammatory Angiotensin 1,7 peptides. Derangements in these peptides are associated with cardiovascular disease and are implicated in the progression of acute respiratory distress syndrome (ARDS). Augmentation of the ACE2/Ang1,7 axis represent a critical target in the supportive management of COVID-19 associated lung disease. Observational data describing the use of RAAS inhibitors in the setting of SARS-CoV-2 have not borne signals of harm to date. However, equipoise persists requiring an analysis of novel agents including recombinant human-ACE2 and existing RAAS inhibitors while balancing ongoing controversies associated with increased coronavirus infectivity and virulence.


2021 ◽  
Vol 4 (Special2) ◽  
pp. 389-394
Author(s):  
Angela Madalina Lazar

Currently, there is a persisting dispute regarding the renin-angiotensin-aldosterone-system (RAAS) inhibitors' safety of use in COVID-19 pandemics. On one side, RAAS inhibitors appear to determine an overexpression of ACE2, the receptor of SARS-CoV-2. Therefore, they could increase the risk of SARS-CoV-2 infection and its degree of severity. On the other side, the discontinuation of RAAS leads to cardiovascular decompensation and has been discouraged by the major medical societies. Also, large-cohort studies report beneficial or at least neutral effects for the RAAS inhibitors in COVID-19 patients. Worldwide, millions of patients receive RAAS inhibitors for the treatment of hypertension and other important comorbidities. In this context, knowledge of the exact effect of these medications becomes of crucial significance. This paper aims to fill in a gap in the current knowledge and presents a putative mechanism by which RAAS inhibitor administration's beneficial results can be explained better. RAAS inhibitors can be beneficial, as they counteract the excessive detrimental activation of the classical angiotensin-converting enzyme (ACE) axis, decreasing the angiotensin II levels. The angiotensin receptor blockers (ARBs) increase the angiotensin II levels, while the angiotensin-converting enzyme inhibitors (ACEI) increase the angiotensin I levels; these substrates will compete with the SARS-CoV-2 for the ACE2 binding, decreasing the viral infectivity. In addition, following the RAAS inhibitors treatment, the up-regulated ACE2 will cleave these substrates (angiotensin I and II), particularly to angiotensin 1-7 that possesses vasodilator, protective effects.


2021 ◽  
Author(s):  
Alexander Kutz ◽  
Anna Conen ◽  
Claudia Gregoriano ◽  
Sebastian Haubitz ◽  
Daniel Koch ◽  
...  

Objective While evidence on the interface between severe acute respiratory syndrome-coronavirus-2 (SARS-CoV-2) infection and the renin-angiotensin-aldosterone-system (RAAS) is accumulating, clinical data on RAAS peptide alteration among coronavirus disease-19 (COVID-19) patients is missing. Design and Methods In this exploratory study, we prospectively included adult patients (aged ≥18 years) admitted between February 26 and April 30, 2020 to a tertiary care hospital in Switzerland. We assessed the association of an underlying SARS-CoV-2 infection and equilibrium serum levels of RAAS peptides in hospitalized COVID-19 patients 1:1 propensity-score matched with patients suffering from SARS-CoV-2-negative respiratory infections. Subgroup analyses involved stratification for taking RAAS inhibitors. Results COVID-19 patients had about 50% lower equilibrium serum RAAS peptide levels as compared with matched controls (angiotensin I: 31.6 vs. 66.8pmol/l, -52.7% [95%CI -68.5% to -36.9%]; angiotensin II: 37.7 vs. 92.5pmol/l, -59.2% [95%CI -72.1% to -46.3%]; angiotensin (1-5): 3.3 vs. 6.6pmol/l, -49.7% [95%CI -59.2% to -40.2%]; angiotensin (1-7): 4.8 vs. 7.6pmol/l, -64.9% [95%CI -84.5% to -45.3%]). While the plasma renin activity (PRA-S) was lower in COVID-19 patients (88.6 vs. 207.9pmol/l, -58.5% [95%CI -71.4% to -45.6%]), there was no difference of angiotensin-converting enzyme (ACE) and ACE2 plasma activity between the groups. Subgroup analyses revealed a pronounced RAAS peptide profile depression in COVID-19 patients among those not on RAAS inhibitors. Conclusions As compared with SARS-CoV-2-negative patients, we found a downregulated RAAS in presence of a SARS-CoV-2 infection. Whether the lower levels of the protective angiotensin (1-5) and (1-7) are linked to adverse outcomes in COVID-19 warrants further investigation.


Hypertension ◽  
2020 ◽  
Vol 75 (2) ◽  
pp. 483-491 ◽  
Author(s):  
Wan-Ting Hsu ◽  
Brandon Patrick Galm ◽  
Gregory Schrank ◽  
Tzu-Chun Hsu ◽  
Shih-Hao Lee ◽  
...  

Antagonists of the renin-angiotensin-aldosterone system (RAAS), including ACEIs (angiotensin-converting enzyme inhibitors) and ARBs (angiotensin II receptor blockers), may prevent organ failure. We, therefore, investigated whether specific RAAS inhibitors are associated with reduced mortality in patients with sepsis.We conducted a population-based retrospective cohort study using multivariable propensity score–based regression to control for differences among patients using different RAAS inhibitors. A multivariable-adjusted Cox proportional-hazards regression model was used to determine the association between RAAS inhibitors and sepsis outcomes. To directly compare ACEI users, ARB users, and nonusers, a 3-way propensity score matching approach was performed. Results were pooled with previous evidence via a random-effects meta-analysis. A total of 52 727 patients were hospitalized with sepsis, of whom 7642 were prescribed an ACEI and 4237 were prescribed an ARB. Using propensity score–matched analyses, prior ACEI use was associated with decreased 30-day mortality (hazard ratio, 0.84 [95% CI, 0.75–0.94]) and 90-day mortality (hazard ratio, 0.83 [95% CI, 0.75–0.92]) compared with nonuse. Prior ARB use was associated with an improved 90-day survival (hazard ratio, 0.88 [95% CI, 0.83–0.94]). These results persisted in sensitivity analyses focusing on patients without cancer and patients with hypertension. By contrast, no beneficial effect was found for antecedent β-blockers exposure (hazard ratio, 0.99 [95% CI, 0.94–1.05]). The pooled estimates obtained from the meta-analysis was 0.71 (95% CI, 0.58–0.87) for prior use of ACEI/ARB.The short-term mortality after sepsis was substantially lower among those who were already established on RAAS inhibitor treatment when sepsis occurred.


Hypertension ◽  
2020 ◽  
Vol 76 (3) ◽  
pp. 732-741 ◽  
Author(s):  
Wei Pan ◽  
Jishou Zhang ◽  
Menglong Wang ◽  
Jing Ye ◽  
Yao Xu ◽  
...  

Hypertension is one of the most common comorbidities in patients with coronavirus disease 2019 (COVID-19). This study aimed to clarify the impact of hypertension on COVID-19 and investigate whether the prior use of renin-angiotensin-aldosterone system (RAAS) inhibitors affects the prognosis of COVID-19. A total of 996 patients with COVID-19 were enrolled, including 282 patients with hypertension and 714 patients without hypertension. Propensity score-matched analysis (1:1 matching) was used to adjust the imbalanced baseline variables between the 2 groups. Patients with hypertension were further divided into the RAAS inhibitor group (n=41) and non-RAAS inhibitor group (n=241) according to their medication history. The results showed that COVID-19 patients with hypertension had more severe secondary infections, cardiac and renal dysfunction, and depletion of CD8 + cells on admission. Patients with hypertension were more likely to have comorbidities and complications and were more likely to be classified as critically ill than those without hypertension. Cox regression analysis revealed that hypertension (hazard ratio, 95% CI, unmatched cohort [1.80, 1.20–2.70]; matched cohort [2.24, 1.36–3.70]) was independently associated with all-cause mortality in patients with COVID-19. In addition, hypertensive patients with a history of RAAS inhibitor treatment had lower levels of C-reactive protein and higher levels of CD4 + cells. The mortality of patients in the RAAS inhibitor group (9.8% versus 26.1%) was significantly lower than that of patients in the non-RAAS inhibitor group. In conclusion, hypertension may be an independent risk factor for all-cause mortality in patients with COVID-19. Patients who previously used RAAS inhibitors may have a better prognosis.


2021 ◽  
Author(s):  
ARTHUR FIOROTTO DE MATTOS ◽  
NATHALIA SILVEIRA BARSOTTI ◽  
RAFAEL RIBEIRO ALMEIDA

The world faces today a pandemic of unquestionable importance, caused by an infection with a new enveloped RNA virus that belongs to the Coronaviridae family. The new coronavirus (SARS-CoV 2) uses a glycoprotein present on its surface to bind to and infect host cells that express the angiotensin converting enzyme II (ACE-2). Although different tissues may be targeted by the virus, respiratory complications remain as the main cause of death. It has been demonstrated that Renin-Angiotensin-Aldosterone System (RAAS) inhibitors increase ACE-2 expression in animal models, raising the concern that patients under treatment with these drugs could become more susceptible to COVID-19 complications. Here, we discuss the impact of RAAS inhibitors on COVID-19 outcomes and show that no evidence so far supports that the use of these drugs could pose a risk to SARS-CoV 2-infected patients. In fact, clinical data suggest that RAAS inhibitors may even act in a protective way against COVID-19 complications and should not be discontinued.,


CNS Spectrums ◽  
2010 ◽  
Vol 15 (11) ◽  
pp. 619-629 ◽  
Author(s):  
Elisavet Moutzouri ◽  
George Daios ◽  
Moses Elisaf ◽  
Haralampos J. Milionis

AbstractThe renin angiotensin aldosterone system (RAAS) has been implicated in the pathogenesis of cerebrovascular diseases. During the past decades, AU: INCLUDE A NUMBER? RAAS has gained attention as an important therapeutic target in cardiovascular medicine. Modulation of the RAAS for primary and secondary stroke prevention seems an appealing strategy. Several experimental studies have showed that pre-treatment with RAAS inhibitors prior to the initiation of ischemia exerts favorable effects on infarct volume, brain edema, and cerebral blood flow in the marginal zone. Furthermore, the activation of angiotensin receptor type 2 has been associated with neuroprotective effects. Accumulating evidence based on recent clinical trials indicate that blockade of RAAS has a potential role in stroke prevention. This review summarizes the pathophysiological aspects of brain RAAS and its constituents, presents experimental data on the neuroprotective actions of RAAS inhibitors and available evidence regarding their effects on stroke risk, and discuss future directions for research.


2020 ◽  
Author(s):  
Yihienew M. Bezabih ◽  
Alemayehu Bezabih ◽  
Endalkachew Aalamneh ◽  
Gregory M. Peterson ◽  
Woldesellassie M. Bezabhe

AbstractIntroductionThe effects of renin–angiotensin–aldosterone system (RAAS) inhibitors on the clinical outcomes of coronavirus disease-19 (COVID-19) have been conflicting in different studies. This meta-analysis was undertaken to provide more conclusive evidence.MethodsA systematic search for published articles was performed in PubMed and EMBASE from January 5 2020 till May 5 2020. Studies that reported the clinical outcomes of patients with COVID-19, stratified by the class of concomitant antihypertensive drug therapy, were included. The Mantel-Haenszel random effects model was used to estimate pooled odds ratio (OR).ResultsA total of 6,997 patients with COVID-19 were included, and all of them had hypertension. The overall risk of poor patient outcomes (severe COVID-19 or death) was lower in patients taking RAAS inhibitors (OR=0.84, 95% CI: [0.73, 0.96]; P=0.017) compared with those receiving non-RAAS inhibitor antihypertensives. Patients taking angiotensin-I-converting enzyme inhibitors (ACEIs) were less likely to experience poor clinical outcomes (OR=0.73, 95% CI: [0.58-0.92]; P=0.01) compared with those receiving angiotensin-II receptor blockers (ARBs). In addition, comparison of ACEIs to the rest of non-ACEI antihypertensives gave a consistently decreased risk of poor COVID-19 outcome (OR=0.77, 95% CI: [0.63-0.93]; P=0.002). However, ARBs did not decrease the risk of poor COVID-19 outcomes compared to all other non-ARB antihypertensives (OR=1.13, 95% CI: [0.95-1.35]).ConclusionThe risk of developing severe illness or death from COVID-19 was lower in patients who received RAAS inhibitors compared with those who took non-RAAS inhibitors. ACEIs might be better in decreasing the severity and mortality of COVID-19 than ARBs.


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