A Meta-analysis of the Relationship Between Renin-Angiotensin-Aldosterone System Inhibitors and COVID-19

Usman, Muhammad; Siddiqi, Tariq Jamal; Khan, Muhammad Shahzeb; Ahmed, Areeba; Ali, Syed Atif; Michos, Erin D.; Hall, Michael E.; Krasuski, Richard A.; Greene, Stephen J.; Butler, Javed; Alkhouli, Mohamad

doi:10.1016/j.amjcard.2020.05.038

Cited by 23 publications

(36 citation statements)

References 8 publications

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“…In fact, in our random-effects meta-analysis of studies that provided adjusted mortality estimates, we observed significantly lower risk of mortality with the use of ACEIs/ARBs in COVID-19 patients relative to non-use of ACEIs/ARBs. Our findings are in line with previously reported meta-analyses [96][97][98][99][100] with unadjusted estimates that demonstrated no increased risk of mortality with the use of ACEIs/ARBs in COVID-19 patients.…”

Section: Discussionsupporting

confidence: 93%

“…Since previous meta-analyses [96][97][98][99][100][101][102] included a majority of studies from China, the generalizability of their findings to patient populations from other regions was also questioned. In the present study, we observed no regional difference with regard to mortality estimates, where separate pooled analyses of studies from East Asian countries, European countries, and the United States, respectively, did not find an increased risk of mortality with the use of ACEIs/ ARBs.…”

Section: Discussionmentioning

confidence: 99%

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Mortality and Disease Severity Among COVID-19 Patients Receiving Renin-Angiotensin System Inhibitors: A Systematic Review and Meta-analysis

Hasan

Kow

Hadi

et al. 2020

Am J Cardiovasc Drugs

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Introduction The use of renin-angiotensin system (RAS) inhibitors, including angiotensin-converting enzyme inhibitors (ACEIs) and angiotensin receptor blockers (ARBs), was alleged to cause a more severe course of novel coronavirus disease 2019 (COVID-19). Methods We systematically reviewed the published studies to assess the association of RAS inhibitors with mortality as well as disease severity in COVID-19 patients. A systematic literature search was performed to retrieve relevant original studies investigating mortality and severity (severe/critical disease) in COVID-19 patients with and without exposure to RAS inhibitors. Results A total of 59 original studies were included for qualitative synthesis. Twenty-four studies that reported adjusted effect sizes (24 studies reported mortality outcomes and 16 studies reported disease severity outcomes), conducted in RAS inhibitor-exposed and unexposed groups, were pooled in random-effects models to estimate overall risk. Quality assessment of studies revealed that most of the studies included were of fair quality. The use of an ACEI/ARB in COVID-19 patients was significantly associated with lower odds (odds ratio [OR] = 0.73, 95% confidence interval [CI] 0.56-0.95; n = 18,749) or hazard (hazard ratio [HR] = 0.75, 95% CI 0.60-0.95; n = 26,598) of mortality compared with non-use of ACEI/ARB. However, the use of an ACEI/ARB was non-significantly associated with lower odds (OR = 0.91, 95% CI 0.75-1.10; n = 7446) or hazard (HR = 0.73, 95% CI 0.33-1.66; n = 6325) of developing severe/critical disease compared with non-use of an ACEI/ARB. Discussion Since there was no increased risk of harm, the use of RAS inhibitors for hypertension and other established clinical indications can be maintained in COVID-19 patients.

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Section: Discussionsupporting

confidence: 93%

Section: Discussionmentioning

confidence: 99%

Mortality and Disease Severity Among COVID-19 Patients Receiving Renin-Angiotensin System Inhibitors: A Systematic Review and Meta-analysis

Hasan

Kow

Hadi

et al. 2020

Am J Cardiovasc Drugs

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“…We included eight studies with a minimum sample size of 100 participants, which allowed us to analyze 17943 patients. Our findings, while having moderate to high heterogeneity, have been in line with other recently published data, which also did not reveal a signal for harm associated with exposure to ACEi/ARBs in COVID-19 infection [ 12 - 13 ]. These results further support the AHA, ACC, Centers for Disease Control and Prevention (CDC), and World Health Organization position statements that ACEi/ARBs should be continued in COVID-19 infection in patients already taking them at the time of diagnosis unless another indication for discontinuation is present, other than SARS-COV-2 positivity.…”

Section: Discussionsupporting

confidence: 92%

Renin-Angiotensin-Aldosterone System Inhibitors and COVID-19: A Meta-Analysis and Systematic Review

Hassib¹,

Hamilton²,

Elkhouly³

et al. 2021

Cureus

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Introduction Increased virulence, the severity of illness, and mortality have all been hypothesized with respect to angiotensin-converting enzyme inhibitor (ACEi)/angiotensin receptor blocker (ARB) use in coronavirus disease 2019 (COVID-19) infection. Our study aims to assess whether ACEi/ARB use in patients with COVID-19 conferred worsened severity of illness or increased mortality. Additionally, we explore the possibility of an unearthed protective benefit due to their interruption of the RAS signaling pathway as observed in cardiovascular diseases. Methods The Cochrane Library, MEDLINE, and EMBASE were searched for studies relevant to COVID-19 severity, mortality, and inflammation in the context of ACEi/ARB use. Eight studies were included with a total of 17,943 patients, 4,292 (23.9%) of which were taking an ACEi or an ARB. The study population was 47.9% female and the average age across all studies was 65. The studies chosen had a sample size of at least 100 patients. Results Mortality outcomes were assessed in six studies and showed no significant difference in mortality among the ACEi/ARB and control groups (odds ratio [OR]: 0.99, 95%CI: 0.48-2.04). Seven studies assessed the severity of COVID-19 and showed no statistically significant difference in disease severity when comparing the ACEi/ARB group to the control group (odds ratio [OR]: 1.30, 95% CI 0.87-1.94). Four studies reported the length of stay with no significant difference between the ACEi/ARB groups as compared to non-users. Four studies included inflammatory markers C-reactive protein (CRP) and D-Dimer, which were noted to be consistently lower in the ACEi/ARB groups when compared to control groups, however, this was not statistically significant. Conclusion Our study found no significant difference in mortality, severity of illness, or length of stay between ACEi/ARB users and non-users with COVID-19 infection. These results support the continuation of ACEi and ARBs in the setting of COVID-19 as advised by the American College of Cardiology (ACC)/American Heart Association (AHA). The decrease in CRP and D-dimer suggests a possible protective effect related to ACEi/ARB use in COVID-19, however, more studies with larger sample sizes are needed to establish this effect.

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“…A recent meta-analysis by Usman et al showed no association between RAASb use and mortality in COVID-19 patients. However, there was lack of data regarding the separate use of angiotensin-converting enzyme inhibitors (ACEIs) and angiotensin receptor blockers (ARBs) and adjusted data was reported by only one study [ 7 ].…”

Section: Introductionmentioning

confidence: 99%

Renin-Angiotensin-Aldosterone System Blockers Prior to Hospitalization and Their Association With Clinical Outcomes in Coronavirus Disease 2019 (COVID-19)

Banwait¹,

Singh²,

Blanco³

et al. 2021

Cureus

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Objective: To determine the effect of angiotensin-converting enzyme inhibitors (ACEIs) and angiotensin receptor blockers (ARBs) use prior to hospitalization on clinical outcomes in coronavirus disease 2019 (COVID-19) patients. Design: An observational retrospective cohort study from 178 hospitals from a large health system across the United States. Patient population: Hospitalized patients (n=2726) with confirmed COVID-19 between January 1, 2020, and April 1, 2020. Main outcome(s) and measure(s): Outcomes during hospitalization, including disease severity by level of care, intensive care unit (ICU) admission, mechanical ventilator (MV) use, hospital length of stay, and in-hospital death. Patient demographics and comorbidities were also recorded. Results: A total of 2,726 patients were included in the analysis. Three hundred ninety-eight (14.6%) patients were taking an ACEI, while 352 (12.9%) patients were taking an ARB prior to hospitalization. After adjusting for comorbidities, age, renal function, and severity of illness based on level of care, ACEI prior to admission was independently associated with decreased need for MV (odds ratio [OR] 0.56, p value 0.003) and mortality (OR 0.45, p value <0.001). Similarly, patients who took ARBs were less likely to require MV when compared to the non-renin-angiotensin-aldosterone system blockade (RAASb) group (7.4% vs 12.2%, p value 0.009, respectively). ARB prior to admission was also independently associated with decreased need for MV (OR 0.46, p value 0.001) and mortality (OR 0.66, p value 0.017) compared to the non-RAASb group. Conclusion: Taking ACEIs and ARBs prior to admission for COVID-19 was independently associated with decreased need for mechanical ventilation and in-hospital mortality.

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A Meta-analysis of the Relationship Between Renin-Angiotensin-Aldosterone System Inhibitors and COVID-19

Cited by 23 publications

References 8 publications

Mortality and Disease Severity Among COVID-19 Patients Receiving Renin-Angiotensin System Inhibitors: A Systematic Review and Meta-analysis

Mortality and Disease Severity Among COVID-19 Patients Receiving Renin-Angiotensin System Inhibitors: A Systematic Review and Meta-analysis

Renin-Angiotensin-Aldosterone System Inhibitors and COVID-19: A Meta-Analysis and Systematic Review

Renin-Angiotensin-Aldosterone System Blockers Prior to Hospitalization and Their Association With Clinical Outcomes in Coronavirus Disease 2019 (COVID-19)

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