COVID-19 Evidence Alerts
from McMaster PLUSTM

Current best evidence for clinical care (more info)

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Etiology Hassib M, Hamilton S, Elkhouly A, et al. Renin-Angiotensin-Aldosterone System Inhibitors and COVID-19: A Meta-Analysis and Systematic Review. Cureus. 2021 Feb 4;13(2):e13124. doi: 10.7759/cureus.13124.

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.

Discipline / Specialty Area Score
Hospital Doctor/Hospitalists
Internal Medicine
Intensivist/Critical Care
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Comments from MORE raters

Hospital Doctor/Hospitalists rater

This is a reasonably solid approach to a systematic review. Some risk of publication bias. However, the evidence supports not stopping pre-existing RAAS blockade in patients subsequently diagnosed with COVID-19 infection.

Intensivist/Critical Care rater

Hassib M et al did a meta-analysis of the correlation of ACEI/ARB in COVID-19 infection. In that, they found concurrent use of these does not alter the course or outcome of COVID-19 infection pattern or mortality. Strengths: 1. This is a well-powered RCTs included in final analysis. 2. There is strict use inclusion and exclusion criteria. Weakness: 1. The strict selection criteria possibly led to missing many relevant studies. 2. The finding of only English language publications also possibly led to this. 3. Analysing only mortality, or the use of severity scores may not reveal all the inflammation indicators. Impression: Good meta-analysis, but these outcomes are already in vogue and much publicized.

Intensivist/Critical Care rater

This is a good review. The topic is very relevant and important. The use of systematic ways in finding and appraising the evidence are the strength of this review. We now more confidence to keep prescribing ARB and ACE inhibitor for our patients.

Respirology/Pulmonology rater

The decrease in CRP and D-dimer as a possible protective effect related to ACEi/ARB use in COVID-19 was a novel finding.