scholarly journals An ISH-led prospective meta-analysis on RCTs of RAAS inhibitors in COVID-19 patients: A call for collaboration

2021 ◽  
Vol 64 ◽  
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.


2021 ◽  
Vol 7 (1) ◽  
Author(s):  
Chinonyerem O. Iheanacho ◽  
Valentine U. Odili ◽  
Uchenna I. H. Eze

Abstract Background Angiotensin-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 body Search 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. Conclusion Evidence 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.


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.


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.


2020 ◽  
Author(s):  
Tamirat Bekele Beressa ◽  
Tamiru Sahilu ◽  
Serawit Deyno

Objective: This research aimed to systematically review and summarize the influence of Renin-Angiotensin-Aldosterone System (RAAS) inhibitors on the outcome of COVID_19 patients with hypertension. Methods: Electronic databases; PubMed/Medline, CINAHL, the Cochrane Central Register of Controlled Trials, clinical trial.gov, and Google Scholar were searched from 2019 to June 1, 2020. Additionally, the references of identified articles were also searched. Results: A total of 9 articles comprising 3,823 patients were incorporated; 1416 patients on RAAS inhibitors and 3469 on non-RAAS inhibitors. The study demonstrated that the taking of RAAS inhibitors in COVID_19 patients with hypertension significantly reduced mortality where patients on RAAS inhibitors had a 27% decrease of mortality (RR= 0.73 [95% CI: 0.63- 0.85, p<0.0001, I2=0%, random-effects model]) compared to those not taking ACEI/ARB. No significant association were observed in disease severity (RR= 0.92 (95% CI: 0.74- 1.14) and hospitalization (WMD= -2.33[95% CI: -5.60, 0.75]), random-effects model. Conclusion: This study supports RAAS inhibitors safe use among COVID_19 patients with hypertension. Keywords: COVID_19, ACEI, ARB, Hypertension, Coronavirus


Author(s):  
Anna Ssentongo ◽  
Paddy Ssentongo ◽  
Emily S. Heilbrunn ◽  
Alain Lekoubou ◽  
Ping Du ◽  
...  

Objective: The association between renin-angiotensin-aldosterone (RAAS) inhibitors and Coronavirus diseases 2019 (COVID-19) mortality is unclear. We aimed to explore the association of RAAS inhibitors, including angiotensin-converting inhibitors (ACEi) and angiotensin II receptor blockers (ARBs) with COVID-19 mortality in patients with hypertension. Methods: MEDLINE, SCOPUS, OVID, and Cochrane Library were searched for the period of January 1, 2020 to May 20, 2020. Studies reporting the association of RAAS inhibitors (ACEi and ARBs) and mortality in patients with hypertension, hospitalized for COVID-19 were extracted. Two reviewers independently extracted appropriate data of interest and assessed the risk of bias. All analyses were performed using random-effects models on log-transformed risk ratio estimates, and heterogeneity was quantified. Results: Data were collected on 2,065,805 individuals (mean age, 58.73 years; 53.4% male). Patients with hypertension taking RAAS inhibitors were 35% less likely to die from COVID-19 compared to patients with hypertension not taking RAAS inhibitors (pooled RR= 0.65, 95% Confidence Intervals (CI): 0.45-0.94). To explore the association of COVID-19 and specific classes of RAAS inhibitors, we conducted a subgroup analysis of ARBs and ACEi separately from studies that provided them. Pooled risk ratio estimates from ARBs and ACEi showed a lower but not significant risk of death from COVID-19 (RR=0.93, 95% CI: 0.70-1.22) and ACEi (RR=0.65, 95% CI: 0.32-1.30). Conclusions: In this meta-analysis, it was discovered that taking RAAS inhibitors, significantly decreased the risk of COVID-19 mortality in patients with hypertension. This indicates a potential protective role that RAAS-inhibitors may have in COVID-19 patients with hypertension.


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.


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