RENIN-ANGIOTENSIN-ALDOSTERONE SYSTEM INHIBITORS AND COVID-19 COMPLICATIONS

2021 ◽  
Author(s):  
ARTHUR FIOROTTO DE MATTOS ◽  
NATHALIA SILVEIRA BARSOTTI ◽  
RAFAEL RIBEIRO ALMEIDA
Keyword(s):  
Rna Virus ◽  
Host Cells ◽  
Converting Enzyme ◽  
Respiratory Complications ◽  
Renin Angiotensin Aldosterone System ◽  
Renin Angiotensin ◽  
The World ◽  
Raas Inhibitors ◽  
The Impact ◽  
Different Tissues

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.,

scholarly journals Renin-angiotensin-aldosterone system inhibitors – a realm of confusion in COVID-19

2021 ◽  
Vol 4 (Special2) ◽  
pp. 389-394
Author(s):  
Angela Madalina Lazar
Keyword(s):  
Angiotensin Ii ◽  
Angiotensin Converting Enzyme ◽  
Current Knowledge ◽  
Angiotensin Receptor Blockers ◽  
Protective Effects ◽  
Converting Enzyme ◽  
Angiotensin I ◽  
Renin Angiotensin Aldosterone System ◽  
Renin Angiotensin ◽  
Raas Inhibitors

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.

scholarly journals Clinical Features of COVID-19 in Patients With Essential Hypertension and the Impacts of Renin-angiotensin-aldosterone System Inhibitors on the Prognosis of COVID-19 Patients

Hypertension ◽  
2020 ◽  
Vol 76 (3) ◽  
pp. 732-741 ◽  
Author(s):  
Wei Pan ◽  
Jishou Zhang ◽  
Menglong Wang ◽  
Jing Ye ◽  
Yao Xu ◽  
...  
Keyword(s):  
Cox Regression ◽  
Medication History ◽  
Renin Angiotensin Aldosterone System ◽  
Cox Regression Analysis ◽  
Renin Angiotensin ◽  
Reactive Protein ◽  
All Cause Mortality ◽  
History Of ◽  
Raas Inhibitors ◽  
The Impact

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.

scholarly journals Association Between Renin-Angiotensin-Aldosterone System Inhibitors and COVID-19 Infection in South Korea

Hypertension ◽  
2020 ◽  
Vol 76 (3) ◽  
pp. 742-749 ◽  
Author(s):  
Minkook Son ◽  
Jeongkuk Seo ◽  
Sung Yang
Keyword(s):  
South Korea ◽  
Case Control ◽  
Host Cells ◽  
Severe Illness ◽  
National Health Insurance System ◽  
Renin Angiotensin Aldosterone System ◽  
Renin Angiotensin ◽  
Increased Risk ◽  
High Flow Oxygen ◽  
Raas Inhibitors

The severe acute respiratory syndrome coronavirus 2 is known to infect host cells by interacting with ACE2 (angiotensin-converting enzyme 2) expressed in the respiratory epithelium. There have been concerns on whether alterations of ACE2 expression by renin-angiotensin-aldosterone system (RAAS) inhibitors would contribute to the infectivity and severity of coronavirus disease 2019 (COVID-19). We performed a case-control study to investigate the association between RAAS inhibitors and risk and severity of COVID-19 infection in South Korea using the population-based data provided by the Korean National Health Insurance System. Of 16 281 subjects with hypertension, there were 950 (5.8%) confirmed COVID-19 cases. After case-control matching, multivariable-adjusted conditional logistic regression analysis was performed. The adjusted odds ratio and 95% CIs for COVID-19 infection and long-term hospitalization comparing exposure to RAAS inhibitors and nonexposure to RAAS inhibitors was 1.161 (0.958–1.407) and 0.863 (0.533–1.397), respectively. When comparing exposure to RAAS inhibitors and nonexposure to RAAS inhibitors for intensive care unit admission, high-flow oxygen therapy, and death, the adjusted odds ratios (95% CIs) were 1.515 (0.402–5.701), 0.663 (0.272–1.619), and 1.363 (0.513–3.662), respectively. In all analyses, P values were not significant ( P >0.05). The present study demonstrates the absence of an identifiable association between the exposure to RAAS inhibitors and risk and severity of COVID-19 infection, supporting the current medical guidelines and recommendations that patients should not discontinue RAAS inhibitors out of a concern that they are at increased risk for infection or severe illness of COVID-19.

scholarly journals The effect of renin–angiotensin–aldosterone system inhibitors on organ-specific ace2 expression in zebrafish and its implications for COVID-19

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Gha-hyun J. Kim ◽  
Adam Melgoza ◽  
Fei Jiang ◽  
Su Guo
Keyword(s):  
Pcr Analysis ◽  
Specific Information ◽  
Renin Angiotensin Aldosterone System ◽  
Angiotensin Converting Enzyme 2 ◽  
Renin Angiotensin ◽  
Organ Specific ◽  
Vertebrate Model ◽  
Potential Risks ◽  
Raas Inhibitors ◽  
The Impact

AbstractAmong cases of SARS-CoV-2 infections that result in serious conditions or death, many have pre-existing conditions such as hypertension and are on renin–angiotensin–aldosterone system (RAAS) inhibitors. The angiotensin-converting-enzyme-2 (ACE2), a key protein of the RAAS pathway, also mediates cellular entry of SARS-CoV-2. RAAS inhibitors might affect the expression levels of ace2, which could impact patient susceptibility to SARS-CoV-2. However, multi-organ-specific information is currently lacking and no species other than rodents have been examined. To address this knowledge gap, we treated adult zebrafish with the RAAS inhibitors aliskiren, olmesartan, and captopril for 7 consecutive days and performed qRT-PCR analysis of major RAAS pathway genes in the brain, gill, heart, intestine, kidney, and liver. Both olmesartan and captopril significantly increased ace2 expression in the heart, gill, and kidney. Olmesartan also increased ace2 expression in the intestine. Conversely, aliskiren significantly decreased ace2 expression in the heart. Discontinuation of compound treatments for 7 days did not return ace2 expression to baseline levels. While potential risks or benefits of antihypertensive RAAS inhibitors to SARS-CoV-2 infections in humans remain uncertain, this study provides new insights regarding the impact of RAAS inhibitors on organ-specific ace2 expression in another vertebrate model, thereby providing comparative data and laying scientific groundwork for future clinical decisions of RAAS inhibitor use in the context of COVID-19.

scholarly journals Clinical outcome of renin-angiotensin-aldosterone system blockers in treatment of hypertensive patients with COVID-19: a systematic review and meta-analysis

2021 ◽  
Vol 73 (1) ◽  
Author(s):  
Andrea Laurentius ◽  
Brian Mendel ◽  
Radityo Prakoso
Keyword(s):  
Clinical Outcome ◽  
Angiotensin Converting Enzyme ◽  
Angiotensin Receptor Blockers ◽  
Hospital Treatment ◽  
Main Body ◽  
Converting Enzyme ◽  
Angiotensin Receptor ◽  
Renin Angiotensin Aldosterone System ◽  
Hypertensive Patients ◽  
Renin Angiotensin

Abstract Background Novel coronavirus disease 2019 has been stated as global disease pandemic due to its rapid spread worldwide. Up to 30% of coronavirus disease 2019 patients with hypertension are more susceptible to death. Angiotensin-converting enzyme inhibitors and angiotensin receptor blockers have been used as primary line of medication for hypertension; nonetheless, conflicting data arises as numerous studies showed contradictory results. Main body Aiming to show clinical outcome of renin-angiotensin-aldosterone system blockers in hospital treatment of hypertensive patients with coronavirus disease 2019, systematically searched literatures through five databases were intensively appraised using The Grading of Recommendations Assessment, Development and Evaluation checklists for cohort studies. Based on the result evaluation from retrospective cohorts involving more than 15,000 patients across Asia and other regions of the world, ten encompassed studies divided into two subgroups in this meta-review showed that in-hospital hypertensive coronavirus disease 2019 patients receiving antihypertensive drugs were associated with overall risk reduction in subgroup 1 (hazard ratio, HR = 0.96, 95% CI = 0.82–1.12) to no outcome association of all-cause mortalities in subgroup 2 (HR = 0.26, 95% CI = 0.19–0.34). All appraised studies in synergism showed that mortality outcomes were not augmented with the employment of either ACE inhibitor or ARB in subjects. Conclusion Therefore, the results support recommendation by the American Heart Association not to discontinue angiotensin-converting enzyme inhibitor or angiotensin receptor blocker regimens in coronavirus disease 2019 patients with hypertension.

scholarly journals Renin Angiotensin Aldosterone System Antagonism in 2019 Novel Coronavirus Acute Lung Injury

2021 ◽  
Author(s):  
Davide Ventura ◽  
Amy L Carr ◽  
R Duane Davis ◽  
Scott Silvestry ◽  
Linda Bogar ◽  
...  
Keyword(s):  
Angiotensin Ii ◽  
Angiotensin Ii Receptor ◽  
Pulmonary Tissue ◽  
Renin Angiotensin Aldosterone System ◽  
Angiotensin Converting Enzyme 2 ◽  
Renin Angiotensin ◽  
Receptor Blockers ◽  
Membrane Bound ◽  
Raas Inhibitors ◽  
Novel Coronavirus

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.

scholarly journals Associations Between the Use of Renin–Angiotensin System Inhibitors and the Risks of Severe COVID-19 and Mortality in COVID-19 Patients With Hypertension: A Meta-Analysis of Observational Studies

2021 ◽  
Vol 8 ◽  
Author(s):  
Xiao-Ce Dai ◽  
Zhuo-Yu An ◽  
Zi-Yang Wang ◽  
Zi-Zhen Wang ◽  
Yi-Ren Wang
Keyword(s):  
Angiotensin Converting Enzyme ◽  
Observational Studies ◽  
Meta Analysis ◽  
Severe Disease ◽  
Host Cells ◽  
Cochrane Library ◽  
Converting Enzyme ◽  
Significant Difference ◽  
Duration Of Hospitalization ◽  
The Impact

Angiotensin-converting enzyme inhibitors (ACEIs) and angiotensin receptor blockers (ARBs) share a target receptor with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). The use of ACEIs/ARBs may cause angiotensin-converting enzyme 2 receptor upregulation, facilitating the entry of SARS-CoV-2 into host cells. There is concern that the use of ACEIs/ARBs could increase the risks of severe COVID-19 and mortality. The impact of discontinuing these drugs in patients with COVID-19 remains uncertain. We aimed to assess the association between the use of ACEIs/ARBs and the risks of mortality and severe disease in patients with COVID-19. A systematic search was performed in PubMed, EMBASE, Cochrane Library, and MedRxiv.org from December 1, 2019, to June 20, 2020. We also identified additional citations by manually searching the reference lists of eligible articles. Forty-two observational studies including 63,893 participants were included. We found that the use of ACEIs/ARBs was not significantly associated with a reduction in the relative risk of all-cause mortality [odds ratio (OR) = 0.87, 95% confidence interval (95% CI) = 0.75–1.00; I2 = 57%, p = 0.05]. We found no significant reduction in the risk of severe disease in the ACEI subgroup (OR = 0.95, 95% CI = 0.88–1.02, I2 = 50%, p = 0.18), the ARB subgroup (OR = 1.03, 95% CI = 0.94–1.13, I2 = 62%, p = 0.48), or the ACEI/ARB subgroup (OR = 0.83, 95% CI = 0.65–1.08, I2 = 67%, p = 0.16). Moreover, seven studies showed no significant difference in the duration of hospitalization between the two groups (mean difference = 0.33, 95% CI = −1.75 to 2.40, p = 0.76). In conclusion, the use of ACEIs/ARBs appears to not have a significant effect on mortality, disease severity, or duration of hospitalization in COVID-19 patients. On the basis of the findings of this meta-analysis, there is no support for the cessation of treatment with ACEIs or ARBs in patients with COVID-19.

Analysing the impact of a guideline for the use of new potassium binders for treatment of chronic hyperkalaemia to maximise inhibition of renin–angiotensin–aldosterone system (RAAS) within the general nephrology clinic?

2020 ◽  
Author(s):  
Priyank Patel ◽  
Andrew Frankel
Keyword(s):  
Chronic Kidney Disease ◽  
Kidney Disease ◽  
Renin Angiotensin Aldosterone System ◽  
Renin Angiotensin ◽  
Ckd Stage ◽  
The Mean ◽  
Potassium Binders ◽  
The Impact ◽  
Chronic Use

Abstract Background Renin–angiotensin–aldosterone system (RAAS) inhibitors provide significant cardiorenal benefits with improved long-term outcomes for patients. This is most significant for patients receiving maximal RAAS inhibition, but some patients are unable to tolerate this therapy because of hyperkalaemia. Recently published National Institute for Health and Care Excellence (NICE) technology appraisal guidance recommended using sodium zirconium cyclosilicate (SZC) and patiromer for patients with chronic kidney disease (CKD) stage 3b to 5 or heart failure with reduced ejection fraction, who are not taking an optimised dosage of RAAS inhibitor because of hyperkalaemia. Objective Determine the impact of a locally produced guideline on effective implementation of NICE recommendation for use of SZC or patiromer to help maximise inhibition of the renin–angiotensin–aldosterone system within the general nephrology clinic. Methods A local guideline to practically support the implementation of recommendations made by NICE in the chronic use of new potassium binders was produced. One hundred sequential patients in a general nephrology clinic with non-immune chronic kidney disease (CKD 3 to 5) had their electronic records reviewed. Those with an indication for RAAS inhibition were identified. Results Of the 100 consecutive patients audited, 46 were female and 54 were male. The mean age of these patients was 64 and the mean estimated glomerular filtration rate (eGFR) was 33. Sixty-eight patients had an indication for being on RAAS inhibition with only 10 on maximal doses. Of the remaining 58 patients, 26 (45%) were limited by hyperkalaemia. Of these 26 patients, 12 of these patients (46%) had hyperkalaemia associated with an episode of acute kidney injury (AKI). Therefore, 14% of patients attending a general nephrology clinic were identified suitable for SZC and patiromer. Conclusions A significant proportion (14%) of unselected patients attending a general nephrology clinic were not on optimum RAAS inhibition due to hyperkalaemia. These patients would meet the criteria established within a working guideline for the implementation of the chronic use of SZC or patiromer and are likely to attain prognostic long-term benefit by using these new potassium binders to maximise RAAS inhibition. This analysis has implications for renal centres across the UK.

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