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COVID-19 Evidence Alerts
from McMaster PLUSTM

Current best evidence for clinical care (more info)

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Etiology Grover A, Oberoi M A systematic review and meta-analysis to evaluate the clinical outcomes in COVID-19 patients on angiotensin-converting enzyme inhibitors or angiotensin receptor blockers. Eur Heart J Cardiovasc Pharmacother. 2020 Jun 15. pii: 5857623. doi: 10.1093/ehjcvp/pvaa064.

INTRODUCTION: Angiotensin-converting enzyme inhibitors (ACEIs) and angiotensin receptor blockers (ARBs) share their target receptor site with the SARS-CoV-2 virus, that may cause ACE2 receptor up-regulation which raised concerns regarding ACEI and ARB use in COVID-19 patients. However, many medical professional societies recommended their continued use given the paucity of clinical evidence, but there is a need for an updated systematic review and meta-analysis of the latest clinical studies.

METHODS AND RESULTS: A search was conducted on PubMed, Google Scholar, EMBASE, and various preprint servers for studies comparing clinical outcomes and mortality in COVID-19 patients on ACEIs and/or ARBs, and a meta-analysis was performed. A total of 16 studies were included for the review and meta-analysis. There were conflicting findings reported in the rates of severity and mortality in several studies. In a pooled analysis of four studies, there was a statistically non-significant association of ACEI/ARB use with lower odds of developing severe disease vs. non-users [odds ratio (OR) = 0.81, 95% confidence interval (CI): 0.41-1.58, I2=50.52, P-value = 0.53). In a pooled analysis of six studies, there was a statistically non-significant association of ACEI/ARB use with lower odds of mortality as compared with non-users (OR = 0.86, 95% CI = 0.53-1.41, I2 = 79.12, P-value = 0.55).

CONCLUSION: It is concluded that ACEIs and ARBs should be continued in COVID-19 patients, reinforcing the recommendations made by several medical societies. Additionally, the individual patient factors such as ACE2 polymorphisms which might confer higher risk of adverse outcomes need to be evaluated further.

Discipline / Specialty Area Score
Infectious Disease
Intensivist/Critical Care
Family Medicine (FM)/General Practice (GP)
General Internal Medicine-Primary Care(US)
Hospital Doctor/Hospitalists
Internal Medicine
Emergency Medicine
Comments from MORE raters

Emergency Medicine rater

As an emergency doc, the question of how these patients might fare in the course of their hospitalization is relevant, but our decisions about level of care is dictated more by clinical presentation than by history of medications. While this is a thorough and well-done analysis, it's of limited clinical relevance to us.

Intensivist/Critical Care rater

This paper reviews the evidence behind the association between ACEi/ARB use and outcomes in COVID-19. This was a theoretical concern and this paper has low quality evidence to suggest that no changes to usual practice are necessary. For those who missed the original hype about ACE in COVID 19, this article will be puzzling. For the rest, it confirms that the hype was probably unfounded.

Intensivist/Critical Care rater

In normal times, this analysis wouldn't be done since all the data is of low quality (high standard error, minimal randomization, nonsignificant findings, etc.). This study is useful to practicing CCM/Pulm/ID physicians because these molecular mechanisms have been described, but the clinical utility of intervening on the use of ACE-I remains unclear. In light of these low-grade data, the recommendation that ACE-I be continued in those who are on it makes sense. The thought about the implementation of ACE-I in those without a previous indication is of interest, but that recommendation cannot be made. Many critically-ill SARS-CoV-2 infected patients end up hypotensive and in renal failure/acute renal injury. The role of ACE-I in these patients remains as yet unanswered. For many, the ACE-I would be contraindicated, especially when hypotensive or in renal failure or both.

Respirology/Pulmonology rater

This is certainly topical, but I am not sure it tells us much, except to say it appears reasonable to continue ACEI/ARB in the face of Covid19. There is not much confidence behind this advice. As far as I could tell, none of the studies reviewed adjusted or could adjust for comorbidities etc between users of these medications and non users, making comparisons of outcomes between groups uncertain.