scholarly journals Comparison of renin–angiotensin–aldosterone system inhibitors with other antihypertensives in association with coronavirus disease-19 clinical outcomes: systematic review and meta-analysis

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.

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

Abstract Background: Reports on the effects of renin–angiotensin–aldosterone system (RAAS) inhibitors on the clinical outcomes of coronavirus disease-19 (COVID-19) have been conflicting. We performed this meta-analysis to find conclusive evidence. Methods: We searched published articles through PubMed, EMBASE and medRxiv from 5 January 2020 to 3 August 2020. Studies that reported clinical outcomes of patients with COVID-19, stratified by the class of antihypertensives, were included. Random and fixed-effects models were used to estimate pooled odds ratio (OR). Results: A total 36 studies involving 30,795 patients with COVID-19 were included. The overall risk of poor patient outcomes (severe COVID-19 or death) was lower in patients taking RAAS inhibitors (OR=0.79, 95% CI: [0.67, 0.95]) compared with those receiving non-RAAS inhibitor antihypertensives. However, further sub-meta-analysis showed that specific RAAS inhibitors did not show a reduction of poor COVID-19 outcomes when compared with any class of antihypertensive except beta-blockers (BBs). For example, compared to calcium channel blockers (CCBs), neither angiotensin-I-converting enzyme inhibitors (ACEIs) (OR=0.91, 95% CI: [0.67, 1.23]) nor angiotensin-II receptor blockers (ARBs) (OR=0.90, 95% CI: [0.62, 1.33]) showed a reduction of poor COVID-19 outcomes. When compared with BBs, however, both ACEIs (OR=0.85, 95% CI: [0.73, 0.99) and ARBs (OR=0.72, 95% CI: [0.55, 0.94]) showed an apparent decrease in poor COVID-19 outcomes. Conclusions: RAAS inhibitors did not increase the risk of mortality or severity of COVID-19. Differences in COVID-19 clinical outcomes between different class of antihypertensive drugs were likely due to the underlying comorbidities for which the antihypertensive drugs were prescribed.


2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Yihienew M. Bezabih ◽  
Alemayehu Bezabih ◽  
Endalkachew Alamneh ◽  
Gregory M. Peterson ◽  
Woldesellassie Bezabhe

Abstract Background Reports on the effects of renin–angiotensin–aldosterone system (RAAS) inhibitors on the clinical outcomes of coronavirus disease-19 (COVID-19) have been conflicting. We performed this meta-analysis to find conclusive evidence. Methods We searched published articles through PubMed, EMBASE and medRxiv from 5 January 2020 to 3 August 2020. Studies that reported clinical outcomes of patients with COVID-19, stratified by the class of antihypertensives, were included. Random and fixed-effects models were used to estimate pooled odds ratio (OR). Results A total 36 studies involving 30,795 patients with COVID-19 were included. The overall risk of poor patient outcomes (severe COVID-19 or death) was lower in patients taking RAAS inhibitors (OR = 0.79, 95% CI: [0.67, 0.95]) compared with those receiving non-RAAS inhibitor antihypertensives. However, further sub-meta-analysis showed that specific RAAS inhibitors did not show a reduction of poor COVID-19 outcomes when compared with any class of antihypertensive except beta-blockers (BBs). For example, compared to calcium channel blockers (CCBs), neither angiotensin-I-converting enzyme inhibitors (ACEIs) (OR = 0.91, 95% CI: [0.67, 1.23]) nor angiotensin-II receptor blockers (ARBs) (OR = 0.90, 95% CI: [0.62, 1.33]) showed a reduction of poor COVID-19 outcomes. When compared with BBs, however, both ACEIs (OR = 0.85, 95% CI: [0.73, 0.99) and ARBs (OR = 0.72, 95% CI: [0.55, 0.94]) showed an apparent decrease in poor COVID-19 outcomes. Conclusions RAAS inhibitors did not increase the risk of mortality or severity of COVID-19. Differences in COVID-19 clinical outcomes between different class of antihypertensive drugs were likely due to the underlying comorbidities for which the antihypertensive drugs were prescribed, although adverse effects of drugs such as BBs could not be excluded.


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

Since the effects of renin–angiotensin–aldosterone system (RAAS) inhibitors on the clinical outcomes of coronavirus disease-19 (COVID-19) have been conflicting in different studies, we performed this meta-analysis. A systematic search of published articles was performed in PubMed and EMBASE from January-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). A total of 6,997 hypertensive patients with COVID-19 were included. 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). Compared to all other antihypertensives, ACEIs decreases the risk poor COVID-19 outcomes (OR=0.77, 95% CI: [0.63-0.93]) while ARBs did not (OR=1.13, 95% CI: [0.95-1.35]). The risk of poor patient outcomes from COVID-19 was lower in patients who received RAAS inhibitors compared with those who took non-RAAS inhibitors. Unlike ARBs, ACEIs might help in decreasing the severity and mortality of COVID-19.


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.


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.


2016 ◽  
Vol 29 (4) ◽  
pp. 180-183
Author(s):  
Zbigniew Heleniak ◽  
Zbigniew Zdrojewski ◽  
Piotr Wisniewski ◽  
Leszek Bieniaszewski ◽  
Boleslaw Rutkowski ◽  
...  

Abstract Endothelial dysfunction could be related to the limited availability of nitric oxide (NO). NO is synthesized with the participation of an NO synthase whose activity is inhibited by asymmetric dimethylarginine (ADMA). The synthesis of ADMA is exacerbated by oxidative stress, and several studies have shown the efficacy of drugs acting on the renin-angiotensin-aldosterone system (RAAS) (converting enzyme inhibitors and angiotensin II receptor antagonists) in reducing the level of ADMA. The probable mechanism of drug action is a reduction of oxidative stress through a decrease of angiotensin II formation. The aim of this study was to assess the influence of RAAS blockers on the plasma concentration of ADMA in patients with chronic glomerulonephritis (ChGN). The study included 37 patients, placed into group A and group B, depending on the treatment. Both groups were treated with RAAS blockers. In group B, immunosuppressive drugs were additionally administered. The control visits were at the 0, 6 and 12 months of observation. In both the studied groups (A+B), a significant reduction of ADMA (0.77 vs 0.4 μmol/l; p<0.05) was noticed. In patients suffering from ChGN, the use of RAAS blockers resulted in a significant decrease of plasma ADMA concentration, independently of immunosupressive treatment.


Author(s):  
Ranu Baral ◽  
Maddie White ◽  
Vassilios S Vassiliou

AbstractInhibitors of the Renin-Angiotensin-Aldosterone System (RAAS) notably Angiotensin-Converting Enzyme inhibitors (ACEi) or Angiotensin Receptor Blockers (ARB) have been scrutinised in hypertensive patients hospitalised with coronavirus disease 2019 (COVID-19) following some initial data they might adversely affect prognosis. With an increasing number of COVID-19 cases worldwide and the likelihood of a “second wave” of infection it is imperative to better understand the impact RAAS inhibitor use in antihypertensive covid positive hospitalised patients.A systematic review and meta-analysis of ACEi or ARB in patients admitted with COVID-19 was conducted. PubMed and Embase were searched and six studies were included in the meta-analysis. Pooled analysis demonstrated that 18.3% of the patients admitted with COVID-19 were prescribed ACEi/ARBs (0.183, CI 0.129 to 0.238, p<0.001). The use of RAAS inhibitors did not show any association with ‘critical’ events (Pooled OR 0.833 CI 0.605 to 1.148, p=0.264) or death (Pooled OR 0.650, CI 0.356 to 1.187, p=0.161). In conclusion, our meta-analysis including ‘critical’ events and mortality data on patients prescribed ACEi/ARB and hospitalised with COVID-19, found no evidence to associate ACEi/ARB with death or adverse events.


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