Management of Renin-Angiotensin-Aldosterone System blockade in patients admitted to hospital with confirmed coronavirus disease (COVID-19) infection (The McGill RAAS-COVID- 19): A structured summary of a study protocol for a randomized controlled trial.
Ontology highlight
ABSTRACT:
SUBMITTER: Aflaki M
PROVIDER: S-EPMC7862851 | biostudies-literature | 2021 Feb
REPOSITORIES: biostudies-literature
Publications
Management of Renin-Angiotensin-Aldosterone System blockade in patients admitted to hospital with confirmed coronavirus disease (COVID-19) infection (The McGill RAAS-COVID- 19): A structured summary of a study protocol for a randomized controlled trial.
Aflaki Mona M Flannery Alexandria A Ferreira João Pedro JP Cheng Matthew Pellan MP Kronfli Nadine N Marelli Ariane A Zannad Faiez F Brophy James J Afillalo Jon J Huynh Thao T Giannetti Nadia N Bessissow Amal A Ezekowitz Justin A JA Lopes Renato D RD Ambrosy Andrew P AP Craig Morgan M Sharma Abhinav A
Trials 20210205 1
<h4>Objectives</h4>The aim of the RAAS-COVID-19 randomized control trial is to evaluate whether an upfront strategy of temporary discontinuation of renin angiotensin aldosterone system (RAAS) inhibition versus continuation of RAAS inhibition among patients admitted with established COVID-19 infection has an impact on short term clinical and biomarker outcomes. We hypothesize that continuation of RAAS inhibition will be superior to temporary discontinuation with regards to the primary endpoint of ...[more]
Similar Datasets
Project description:Background and rationaleSome studies of hospitalized patients suggested that the risk of death and/or severe illness due to COVID-19 is not associated with the use of angiotensin-converting enzyme inhibitors (ACEIs) and/or angiotensin II receptor type 1 blockers (ARBs). Nevertheless, some controversy still exists and there is limited information of the ACEIs/ARBs effect size on COVID-19 prognosis.Aim and methodsWe aimed to measure the effect of ACEIs and/or ARBs on COVID-19 severe clinical illness by a meta-analysis. Literature search included all studies published since the COVID-19 outbreak began (December 2019) until May 9, 2020. We analyzed information from studies that included tested COVID-19 patients with arterial hypertension as comorbidity prior to hospital admission and history of taking ACEIs, ARBs, or ACEIs/ARBs.ResultsWe included 16 studies that involved 24,676 COVID-19 patients, and we compared patients with critical (n = 4134) vs. non-critical (n = 20,542) outcomes. The overall assessment by estimating random effects shows that the use of ACEIs/ARBs is not associated with higher risk of in-hospital-death and/or severe illness among hypertensive patients with COVID-19 infection. On the contrary, effect estimate shows an overall protective effect of RAAS inhibitors/blockers (ACEIs, ARBs, and/or ACEIs/ARBs) with ∼ 23 % reduced risk of death and/or critical disease (OR: 0.768, 95%CI: 0.651-0.907, p=0.0018). The use of ACEIs (OR:0.652, 95%CI:0.478-0.891, p=0.0072) but not ACEIs/ARBs (OR:0.867, 95%CI:0.638-1.179, p =NS) or ARBs alone (OR:0.810, 95%CI:0.629-1.044, p=NS) may explain the overall protection displayed by RAAS intervention combined.ConclusionRAAS inhibitors might be associated with better COVID-19 prognosis.
| S-EPMC7255761 | biostudies-literature
Project description:The role of the renin-angiotensin-aldosterone system (RAAS) in many cardiovascular disorders, including hypertension, cardiac hypertrophy, and atherosclerosis, is well established, whereas its relationship with cardiac arrhythmias is a new area of investigation. Atrial fibrillation and malignant ventricular tachyarrhythmias, especially in the setting of cardiac hypertrophy or failure, seem to be examples of RAAS-related arrhythmias because treatment with RAAS modulators, including angiotensin-converting enzyme inhibitors, angiotensin receptor blockers, and mineralocorticoid receptor blockers, reduces the incidence of these arrhythmias. RAAS has a multitude of electrophysiological effects and can potentially cause arrhythmia through a variety of mechanisms. We review new experimental results that suggest that RAAS has proarrhythmic effects on membrane and sarcoplasmic reticulum ion channels and that increased oxidative stress is likely contributing to the increased arrhythmic incidence. A summary of ongoing clinical trials that will address the clinical usefulness of RAAS modulators for prevention or treatment of arrhythmias is presented.
| S-EPMC2600881 | biostudies-literature
Project description:Since the discovery of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), numerous research has been undertaken to delineate the various effects of the virus which manifests in many ways all over the body. The association between the SARS-CoV-2 invasion mechanism and the renin-angiotensin-aldosterone system (RAAS) receptors, created many debates about the possible consequences of using RAAS-modulating drugs including angiotensin-converting enzyme inhibitors (ACEi) and angiotensin II receptor blockers (ARBs) during the pandemic. Many clinical studies were conducted to assess the outcomes of coronavirus disease 2019 (COVID-19) in patients who use ACEi/ARBs following the arguments claiming to discontinue these drugs as a precautionary measure. Although several studies mainly analyzed the outcomes of the disease, this review aimed to compare specific blood markers in both groups of COVID-19 patients to gain better insight into the interaction of ACEi/ARBs with different body functions during the infection. Several databases were searched using a combination of keywords followed by screening and data extraction. Only 28 studies met our inclusion criteria, the majority of which showed no significant difference between the inflammation markers of COVID-19 patients who used or did not use ACEi/ARBs. Interestingly, 6 studies reported lower inflammatory markers in COVID-19 patients who used ACEi/ARBs, and 6 studies reported better outcomes among the same group. We therefore concluded that the use of ACEi/ARBs may not lead to worse prognosis of COVID-19 and may even play a protective role against the hyperinflammatory response associated with COVID-19.
| S-EPMC8014479 | biostudies-literature
Project description:Blockade of the renin-angiotensin-aldosterone system (RAAS) with ACE inhibitors has been a cornerstone of heart failure therapy for over 15 years. More recently, further blockade of RAAS with aldosterone antagonists and angiotensin receptor blockers (ARBs) has been studied. While these therapies have certainly improved outcomes in the treatment of heart failure, morbidity and mortality remain extremely high. Furthermore, polypharmacy and complex regimens of seven medications on average is the norm for management of heart failure. This results in increased costs, patient burden, and uncertainty as to the best course of therapy. The ability to personalize patients' therapeutic regimens using pharmacogenomics has the potential of providing more effective and efficient use of RAAS-modulating medications. This review highlights the implications of major RAAS pharmacogenetic studies, while outlining future directions for translation to practice.
| S-EPMC5013832 | biostudies-literature
Project description:Purpose of reviewThis review summarises the literature data and provides an overview of the role and impact of the use of renin-angiotensin-aldosterone system (RAAS) inhibitors in patients with coronavirus disease 2019 (COVID-19) infection.Recent findingsThe angiotensin-converting enzyme 2 (ACE2) has a key role in the regulation of the RAAS pathway, downregulating angiotensin II and attenuating inflammation, vasoconstriction and oxidative stress. Additionally, it plays an instrumental part in COVID-19 infection as it facilitates the cell entry of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and enables its replication. The use and role of RAAS inhibitors therefore during the COVID-19 pandemic have been intensively investigated. Although it was initially assumed that RAAS inhibitors may relate to worse clinical outcomes and severe disease, data from large studies and meta-analyses demonstrated that they do not have an adverse impact on clinical outcomes or prognosis. On the contrary, some experimental and retrospective observational cohort studies showed a potential protective mechanism, although this effect remains to be seen in large clinical trials.
| S-EPMC9206216 | biostudies-literature
Project description:With the multiplication of COVID-19 severe acute respiratory syndrome cases due to SARS-COV2, some concerns about angiotensin-converting enzyme 1 (ACE1) inhibitors (ACEi) and angiotensin II type 1 receptor blockers (ARB) have emerged. Since the ACE2 (angiotensin-converting enzyme 2) enzyme is the receptor that allows SARS COV2 entry into cells, the fear was that pre-existing treatment with ACEi or ARB might increase the risk of developing severe or fatal severe acute respiratory syndrome in case of COVID-19 infection. The present article discusses these concerns. ACE2 is a membrane-bound enzyme (carboxypeptidase) that contributes to the inactivation of angiotensin II and therefore physiologically counters angiotensin II effects. ACEis do not inhibit ACE2. Although ARBs have been shown to up-regulate ACE2 tissue expression in experimental animals, evidence was not always consistent in human studies. Moreover, to date there is no evidence that ACEi or ARB administration facilitates SARS-COV2 cell entry by increasing ACE2 tissue expression in either animal or human studies. Finally, some studies support the hypothesis that elevated ACE2 membrane expression and tissue activity by administration of ARB and/or infusion of soluble ACE2 could confer protective properties against inflammatory tissue damage in COVID-19 infection. In summary, based on the currently available evidence and as advocated by many medical societies, ACEi or ARB should not be discontinued because of concerns with COVID-19 infection, except when the hemodynamic situation is precarious and case-by-case adjustment is required.
| S-EPMC7172808 | biostudies-literature
Project description:BackgroundAngiotensin-converting-enzyme-2, being the receptor for SARS-CoV-2, is increased in the use of RAAS inhibitors. Therefore, concerns have been raised over risks of SARS-CoV-2 infection and poor prognosis of COVID-19 in persons with prior exposure to these drugs. This study aimed to systematically review available evidence for associations between exposure to RAAS inhibitors with susceptibility to SARS-CoV-2 infection and clinical outcomes in infected persons. It hopes to address the question on the effects of RAAS inhibitors on the risk of COVID-19 and its prognosis.Main bodySearch was conducted in the databases of PubMed, Scopus, Cochrane, Embase and MedRxiv.org from December 2019 to May 31, 2020, using relevant keywords. Additional articles were identified through hand-searching of reference lists. Studies that reported associations between positive tests to COVID-19 and use of RAAS inhibitors, and treatment outcomes of COVID-19 patients who had exposure to RAAS inhibitors were considered eligible. The Newcastle-Ottawa scale was used to assess risk of bias in individual studies. The review was conducted in line with Preferred Regulatory Items for Systematic Reviews and Meta-Analysis (PRISMA) guidelines 2009. From the 952 studies screened and 2 studies from reference hand-searching, 18 were reviewed. Four studies evaluated the risks for SARS-CoV-2 infection among RAAS inhibitors users, and 16 (including 2 of the 4 studies) evaluated the clinical outcomes associated with previous exposure to RAAS inhibitors.ConclusionEvidence does not suggest higher risks for SARS-CoV-2 infection or poor disease prognosis in the use of RAAS inhibitors. This suggests the continued use of RAAS inhibitors by patients with existing needs, which supports the position statements of American Heart Association and European societies for Cardiology.Supplementary informationThe online version contains supplementary material available at 10.1186/s43094-021-00224-4.
| S-EPMC7988641 | biostudies-literature
Project description:BackgroundRenin-angiotensin aldosterone system inhibitors (RAASi) are commonly used among patients hospitalized with a severe acute respiratory syndrome coronavirus 2 infection coronavirus disease 2019 (COVID-19). We evaluated whether continuation versus discontinuation of RAASi were associated with short term clinical or biochemical outcomes.MethodsThe RAAS-COVID-19 trial was a randomized, open label study in adult patients previously treated with RAASi who are hospitalized with COVID-19 (NCT04508985). Participants were randomized 1:1 to discontinue or continue RAASi. The primary outcome was a global rank score calculated from baseline to day 7 (or discharge) incorporating clinical events and biomarker changes. Global rank scores were compared between groups using the Wilcoxon test statistic and the negative binomial test (using incident rate ratio [IRR]) and the intention-to-treat principle.ResultsOverall, 46 participants were enrolled; 21 participants were randomized to discontinue RAASi and 25 to continue. Patients' mean age was 71.5 years and 43.5% were female. Discontinuation of RAASi, versus continuation, resulted in a non-statistically different mean global rank score (discontinuation 6 [standard deviation [SD] 6.3] vs continuation 3.8 (SD 2.5); P = .60). The negative binomial analysis identified that discontinuation increased the risk of adverse outcomes (IRR 1.67 [95% CI 1.06-2.62]; P = .027); RAASi discontinuation increased brain natriuretic peptide levels (% change from baseline: +16.7% vs -27.5%; P = .024) and the incidence of acute heart failure (33% vs 4.2%, P = .016).ConclusionRAASi continuation in participants hospitalized with COVID-19 appears safe; discontinuation increased brain natriuretic peptide levels and may increase risk of acute heart failure; where possible, RAASi should be continued.
| S-EPMC8820148 | biostudies-literature
Project description:BackgroundAngiotensin-converting enzyme inhibitors (ACEi) and angiotensin receptor blockers (ARBs) are two of the most commonly used antihypertensive drugs acting on the renin-angiotensin-aldosterone system (RAAS). Previous research has shown that RAAS inhibitors increase the expression of angiotensin-converting enzyme, a cellular receptor for the severe acute respiratory syndrome coronavirus 2, raising concerns that the use of ACEi and ARBs in hypertensive patients may increase COVID-19 patient mortality. Therefore, the main aim of the current study was to find out the role of drugs acting on RAAS, particularly ACEi/ARBs in the deaths of COVID-19 patients.ResultsIn total, 68 studies were found to be appropriate, reporting a total of 128,078 subjects. The odds ratio was found to be 1.14 [0.95, 1.36], which indicates the non-significant association of ACEi/ARBs with mortality of COVID-19 patients. Further, the association of individual ACEi/ARBs with mortality of COVID-19 patients was also found non-significant. The sensitivity analysis results have shown no significant effect of outliers on the outcome.ConclusionsBased on available evidence, ACEi/ARB were not significantly associated with deaths of COVID-19 patients.
| S-EPMC9448845 | biostudies-literature
Project description:AimsThe severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) binds to the ACE2 component of the renin-angiotensin aldosterone system (RAAS) and infects the human cells. The aims of the present review were to look at the role and alteration of the RAAS components in SARS-CoV-2 infection, therapeutic approaches, and clinical trials in this field.MethodsWe surveyed the literature (PubMed, Web of Science, and Scopus) till August 18, 2021, and 59 published papers regarding the components of the RAAS and their role and alterations in SARS-CoV-2 infection along with various COVID-19 therapies based on the RASS components were included in the study.ResultsACE inhibitors, angiotensin receptor blockers, and mineralocorticoid receptor inhibitors are agents that significantly enhance the ACE2 and Ang-(1-7) levels, which can be suggestive for their role as therapeutics against SARS-CoV-2 infection. Beta-adrenergic blockers, which negatively regulate renin release from juxtaglomerular cells, and vitamin D, as a regulator of the RAAS and renin expression, are proposed therapeutics in the treatment of COVID-19. Some antihyperglycemic agents could be potentially protective against COVID-19-induced lung injury. Also, the inhibition of the Janus kinase/signal transducer and activator of the transcription pathway as a potential treatment for COVID-19 has been suggested. Finally, resveratrol, an antioxidant that can suppress Ang II, has been suggested as an adjunct to other therapies.ConclusionRegarding the suggested potential therapies for COVID-19, there are many clinical trials whose results might change the treatment strategies of SARS-CoV-2 infection. So, the results of well-organized clinical trials on the efficacy and safety of the mentioned agents in the treatment of COVID-19 will be useful in the management and therapy of the disease.
| S-EPMC8596942 | biostudies-literature