Raas Inhibitors
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2021 ◽  
Udo Bonnet ◽  
BenediktBernd Claus ◽  
Martin Schaefer ◽  
Jens Kuhn ◽  
Peter Nyhuis ◽  

Abstract Introduction Several psychiatric and somatic medications are assumed to improve COVID-19-symptoms. These include antidepressants, antipsychotics, and anticonvulsants as well as anticoagulants, statins, and renin-angiotensin-aldosterone-system (RAAS)-inhibitors for somatic comorbid conditions. All these agents may reduce the hyperinflammatory response to SARS/CoV-2 or the related negative cardio-cerebrovascular outcomes. Methods In a retrospective longitudinal, multi-center inpatient study, we sought to explore the influence of psychiatric medications on COVID-19, comprising the period from diagnosing SARS/CoV-2-infection via PCR (nasopharyngeal swab) up to the next 21 days. Ninety-six psychiatric inpatients (mean age [SD] 65.5 (20.1), 54% females) were included. The primary outcome was the COVID-19-duration. Secondary outcomes included symptom severity and the presence of residual symptoms. Results COVID-19-related symptoms emerged in 60 (62.5%) patients, lasting 6.5 days on average. Six (6.3%) 56–95 years old patients died from or with COVID-19. COVID-19-duration and residual symptom-presence (n=22, 18%) were not significantly related to any substance. Respiratory and neuro-psychiatric symptom-load was significantly and negatively related to prescription of antidepressants and anticoagulants, respectively. Fatigue was negatively and positively related to RAAS-inhibitors and proton-pump-inhibitors, respectively. These significant relationships disappeared with p-value adjustment owed to multiple testing. The mean total psychiatric burden was not worsened across the study. Discussion None of the tested medications was significantly associated with the COVID-19-duration and -severity up to the end of post-diagnosing week 3. However, there were a few biologically plausible and promising relationships with antidepressants, anticoagulants, and RAAS-inhibitors before p-value adjustment. These should encourage larger and prospective studies to re-evaluate the influence of somatic and psychiatric routine medications on COVID-19-related health outcomes.

2021 ◽  
Vol 9 (8) ◽  
pp. 1692
Rui Rodrigues ◽  
Sofia Costa de Oliveira

Angiotensin-Converting Enzyme 2 (ACE2) has been proved to be the main host cell receptor for the binding of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the virus responsible for the COVID-19 pandemic. The SARS-CoV-2 spike (S) protein binds to ACE2 to initiate the process of replication. This enzyme is widely present in human organ tissues, such as the heart and lung. The pathophysiology of ACE2 in SARS-CoV-2 infection is complex and may be associated with several factors and conditions that are more severe in COVID-19 patients, such as age, male gender, and comorbidities, namely, cardiovascular diseases, chronic respiratory diseases, obesity, and diabetes. Here we present a comprehensive review that aims to correlate the levels of expression of the ACE2 in patients with comorbidities and with a poor outcome in COVID-19 disease. Significantly higher levels of expression of ACE2 were observed in myocardial and lung tissues in heart failure and COPD patients, respectively. An age-dependent increase in SARS2-CoV-2 receptors in the respiratory epithelium may be also responsible for the increased severity of COVID-19 lung disease in elderly people. Although the role of ACE2 is highlighted regarding the damage that can arise upon the SARS-CoV-2 invasion, there was no association observed between renin-angiotensin-aldosterone system (RAAS) inhibitors and the severity of COVID-19.

Kardiologiia ◽  
2021 ◽  
Vol 61 (7) ◽  
pp. 4-13
V. Yu. Mareev ◽  
L. G. Kapanadze ◽  
G. I. Kheimets ◽  
Yu. V. Mareev

Aim    Optimal combination therapy for chronic heart failure (CHF) currently implies the mandatory use of at least four classes of drugs: renin-angiotensin-aldosterone (RAAS) system inhibitors or angiotensin receptor blocker neprilysin inhibitors (ARNI); beta-adrenoblockers (BAB); mineralocorticoid receptor antagonists; and sodium-glucose cotransporter 2 inhibitors. Furthermore, many of these drugs are able to decrease blood pressure even to hypotension and alleviate tachycardia. This study focused on the relationship of 24-h blood pressure (BP) and heart rate (HR) with the prognosis for CHF patients with sinus rhythm and left ventricular ejection fraction (LV EF) <50 % as well as on suggesting possible variants of safe therapy for CHF depending on the combination of studied factors.Material and methods    Effects of clinical data, echocardiographic parameters, 24-h BP, and heart rhythm (data from 24-h BP and ECG monitors) on the prognosis of 155 patients with clinically pronounced CHF, LV EF <50 %, and sinus rhythm who were followed up for 5 years after discharge from the hospital.Results    The one-factor analysis showed that the prognosis of CHF patients was statistically significantly influenced by the more severe functional class (FC) III CHF compared to FC II, reduced LV EF (<35 %), a lower 24-h systolic BP (SBP) (<103 mm Hg), the absence of hypotensive episodes in daytime, a low variability of nighttime BP (<7.5 mm Hg), a higher 24-h HR (>71 bpm vs. <60 bpm), the absence of therapy with RAAS inhibitors + BAB, and a lower body weight index. The multi-factor analysis showed that more severe CHF FC, lower LV EF, and the absence of RAAS inhibitors + BAB therapy retained the influence on the prognosis. After eliminating the influencing factor of drug therapy, also a low SBP variability significantly influenced the prognosis. An additional analysis determined the following four groups of CHF patients with reduced heart systolic function according to mean 24-h HR and SBP: the largest group (38.1 % of all patients) with controlled HR (≤69 bpm), preserved SBP (>103 mm Hg), and the lowest death rate of 15.3 %; the group with increased HR (>69 bpm) but preserved SBP (30.3 % of all patients) where the death rate was 44.7 %, which was significantly higher than in the first group; the group with normal HR (≤69 bpm) but reduced SBP (≤103 mm Hg) (16.1 % of patients) where the death rate was 40 %, which was comparable with the second group and significantly worse than in the first group; and the group with both increased HR (>69 bpm) and reduced SBP (≤103 mm Hg) (15.5 % of patients), which resulted in the maximal risk of death (70.8 % of patients with CHF and LV EF <50 %), which was significantly higher than in the three other groups.Conclusion    Low SBP (including 24-h SBP with reduced variability in day- and nighttime) in combination with high HR (including by data of Holter monitoring), low LV EF, more severe clinical course of CHF, and the absence of an adequate treatment with neurohormonal modulators (RAAS inhibitors and BAB) significantly increased the risk of death. Isolating four types of FC II-III CHF with sinus rhythm and EF <50% based on the combination of HR and BP identifies patients with an unfavorable prognosis, which will help developing differentiated therapeutic approaches taking into account clinical features.

Jordan Loader ◽  
Erik Lampa ◽  
Stefan Gustafsson ◽  
Thomas Cars ◽  
Johan Sundström

Background Considering the widespread risk of collider bias and confounding by indication in previous research, the associations between renin‐angiotensin aldosterone system (RAAS) inhibitor use and COVID‐19 remain unknown. Accordingly, this study tested the hypothesis that RAAS inhibitors influence the summation effect of COVID‐19 and its progression to severe outcomes. Methods and Results This nationwide cohort study compared all residents of Sweden, without prior cardiovascular disease, in monotherapy (as of January 1, 2020) with a RAAS inhibitor to those using a calcium channel blocker or a thiazide diuretic. Comparative cohorts were balanced using machine‐learning‐derived propensity score methods. Of 165 355 people in the analysis (51% women), 367 were hospitalized or died with COVID‐19 (246 using a RAAS inhibitor versus 121 using a calcium channel blocker or thiazide diuretic; Cox proportional hazard ratio [HR], 0.97; 95% CI, 0.74–1.27). When each outcome was assessed separately, 335 people were hospitalized with COVID‐19 (HR, 0.92; 95% CI, 0.70–1.22), and 64 died with COVID‐19 (HR, 1.22; 95% CI, 0.68–2.19). The severity of COVID‐19 outcomes did not differ between those using a RAAS inhibitor and those using a calcium channel blocker or thiazide diuretic (ordered logistic regression odds ratio, 1.01; 95% CI, 0.89–1.14). Conclusions Despite potential limitations, this study is among the best available evidence that RAAS inhibitor use in primary prevention does not increase the risk of severe COVID‐19 outcomes; presenting strong data from which scientists and policy makers alike can base, with greater confidence, their current position on the safety of using RAAS inhibitors during the COVID‐19 pandemic.

Vishal Madanlal Chaudhari ◽  
Dnyanoba Kishanrao Bhaskar ◽  
Medha Ajit Oak

The renin-angiotensin-aldosterone system (RAAS) is responsible for maintaining hemodynamic stability and thereby impacts multiple organ systems, such as the central nervous system, heart, and kidneys. Angiotensin II (ang II) is the main effector of the RAAS. However, overactivity of the RAAS can give rise to cardiovascular disorders, stroke, and nephrosclerosis. Unfavorable effects on cardiovascular system are attributed to ang II. RAAS activation also results in release and increased activity of several hormonal and inflammatory mediators, trigger formation of a number of secondary messengers and/or activate pathways, which negatively affects blood vessels and tissue. RAAS inhibitors, such as angiotensin-converting enzyme inhibitors (ACEIs), angiotensin receptor blockers (ARBs), and calcium channel blockers can protect various organs from damage by blocking the protean manifestation of RAAS activity, either in its circulating or its locally tissue-active form. This review explains on the pleiotropic effects and benefits that go beyond mere blood pressure control. ACEIs in terms of mortality reduction, long‑term survival benefits, cardioprotective and vasculo-protective effects as well as improve fibrinolytic balance. Ramipril has been clinically proven to reduce rates of mortality, myocardial infarction, and stroke. ACEIs and ARBs were associated with lesser risks of COVID-19 infection.

2021 ◽  
Vol 4 (Special2) ◽  
pp. 389-394
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 ◽  
Vol 10 (14) ◽  
pp. 3147
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.

Kardiologiia ◽  
2021 ◽  
Vol 61 (6) ◽  
pp. 4-10
Yu. V. Mareev ◽  
V. Yu. Mareev

Major principles for treatment of chronic heart failure with reduced left ventricular ejection fraction <40% (HFrEF) include a “triple neurohormonal blockade” as a main approach. However, in recent 6 years, two new classes of drugs for the treatment of HFrEF have appeared, which beneficially influence the prognosis. These drugs are angiotensin receptor neprilysin inhibitors (ARNI) and type 2 sodium-glucose cotransporter 2 (SGLT2) inhibitors.Aim    To compare the net effect of simultaneous treatment with ARNI and SGLT2 inhibitors with the triple neurohormonal blockade in stable or decompensated patients with CHF based on Russian data.Material and methods    We analyzed the risk of death per 100 patient-years in patients with HFrEF. Stable patients were followed up at the A.L. Myasnikov Institute of Cardiology (presently, A.L. Myasnikov Research Institute of Clinical Cardiology of the National Medical Research Center of Cardiology) from 2006 through 2007; data from the EPOCH-Decompensation-CHF study were used for decompensated patients (12.2 % and 36.8 %, respectively).Results    When patients with stable HFrEF were successively switched from renin-angiotensin-aldosterone system (RAAS) inhibitors to ARNI (–16 %) and subsequently supplemented with SGLT2 (–13 %) the risk of death per 100 patient-years decreased from 12.2 % to 8.9 % (total risk decreased by 27 %; to save one patient the ARNI+ SGLT2 combination has to be prescribed to 30 patients). The estimated risk of death upon discharge from the hospital for the patients with decompensated CHF switched from RAAS inhibitors to ARNI (–16 %) and subsequently supplemented with SGLT2 (–13 %) was 26.9 deaths per 100 patient-years, whereas the number of patients to be treated for saving one life was only 10. Based on available data that demonstrate a greater effect of ARNI+ SGLT2 in patients immediately after CHF aggravation, the risk of death was recalculated. According to this analysis, the death rate per 1000 patient-years decreased from 36.8 to 19.9 % (relative risk decrease, 46 %), and to save one life only 6 patients had to be treated after they have achieved compensation of HFrEF.Conclusions    This analysis shows the importance of early initiation of the ARNI+ SGLT2 therapy in patients with both decompensated and with stable HFrEF. 

2021 ◽  
Vol 1-2 (33-34) ◽  
pp. 31-36
І. Dunaieva ◽  
N. Kravchun ◽  

Context. In a pandemic caused by a coronavirus infection, a special risk group are the patients with cardiovascular disease, hypertension and diabetes mellitus in particular, which are the most common risk groups among the general population. The spread of coronavirus disease is particularly dangerous in terms of decompensation of chronic complications, specific damage to the cardiovascular system, especially in cases of severe infection and high risk of adverse outcomes in the above cohort of patients. The combination of coronavirus disease and cardiovascular disease poses additional difficulties in diagnosing, identifying, and prescribing appropriate therapy, including antihypertensive therapy. Therefore, it is important to address the possible risks and complications in people with hypertension and diabetes mellitus in the conditions of coronavirus disease COVID-19 and the features of the antihypertensive therapy prescription. Objective. To investigate the peculiarities of treatment of patients with arterial hypertension in the context of the COVID-19 pandemic, to analyze possible risks and complications based on the results of studying the literature. Materials and methods. Content analysis, methods of systemic and comparative results, as well as bibliosemantic evaluation of current research in the literature on the prescription of antihypertensive therapy in patients with hypertension and diabetes in the conditions of coronavirus COVID-19 were used. Sources of information were searched in scientometric medical databases, namely PubMedNCBI, Medline, Web of Science and Google Scholar, etc. by keywords: diabetes, hypertension, antihypertensive therapy, COVID-19, complications, cardiovascular risk. 174 scientific works in English, Ukrainian and Russian were analyzed and sources were selected, which contain questions about the risks of patients with hypertension and diabetes in the conditions of coronavirus disease, including those related to the appointment of antihypertensive therapy. Results. RAAS inhibitors, which provide better blood pressure control, may partially help to maintain the immune system imbalance in hypertension. In patients with hypertension during a viral infection, blood pressure levels and cardiovascular risk should be monitored. Conclusions. Constant monitoring of hemodynamic parameters, ECG and ECHO-CG – should be under the control according to the indications. The association of RAAS blockers (ACE inhibitors and ARBs) with an increased risk of infection in patients and worsening of COVID-19 has not been established so far, so patients with CVD should continue to take them. Patients who have survived coronavirus disease should be included in the medical rehabilitation programs for faster and better recovery of various systems, primarily respiratory and cardiovascular, as well as to improve quality of life and reduce the risk of disability.

2021 ◽  
Vol 12 ◽  
Elizabeth M. Sajdel-Sulkowska

SARS-CoV-2, primarily considered a respiratory virus, is increasingly recognized as having gastrointestinal aspects based on its presence in the gastrointestinal (GI) tract and feces. SARS-CoV-2 uses as a receptor angiotensin-converting enzyme 2 (ACE-2), a critical member of the renin-angiotensin-aldosterone system (RAAS) involved in the regulation of blood pressure and fluid system. In addition to the systemic endocrine functions, RAAS components are also involved in intracrine and organ-specific local functions. The angiotensin-converting enzyme 2 (ACE-2) is a key component of RAAS and a receptor for SARS-CoV-2. It is expressed in many tissues with gastrointestinal (GI) tract ACE-2 levels far exceeding those in the respiratory tract. SARS-CoV-2 binding to its receptor results in a deficiency of ACE-2 activity in endocrine, intracrine, and local lung and GI tract ACE-2. The local ACE-2 has different organ-specific functions, including hypertension-independent activities; dysregulations of these functions may contribute to multiorgan COVID-19 pathology, its severity, long-term effects, and mortality. We review supporting evidence from this standpoint. Notably, COVID-19 comorbidities involving hypertension, obesity, heart disease, kidney disease, and diabetes are associated with gastrointestinal problems and display ACE-2 deficits. While RAAS inhibitors target both endocrine and intracrine ACE-2 activity, the deficit of the local ACE-2 activity in the lungs and more so in the gut have not been targeted. Consequently, the therapeutic approach to COVID-19 should be carefully reconsidered. Ongoing clinical trials testing oral probiotic bound ACE-2 delivery are promising.

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