COVID-19 Evidence Alerts
from McMaster PLUSTM

Current best evidence for clinical care (more info)

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Etiology Lo KB, Bhargav R, Salacup G, et al. Angiotensin converting enzyme inhibitors and angiotensin II receptor blockers and outcomes in patients with COVID-19: a systematic review and meta-analysis. Expert Rev Cardiovasc Ther. 2020 Dec;18(12):919-930. doi: 10.1080/14779072.2020.1826308. Epub 2020 Oct 5.

BACKGROUND: The use of angiotensin-converting enzyme inhibitors (ACEI) and angiotensin II receptor blockers (ARB) in patients with coronavirus disease 2019 (COVID-19) given their interaction with the angiotensin-converting enzyme-2 (ACE-2) receptor remains controversial. .

OBJECTIVE: To investigate the impact of ACEI/ARB on COVID-19 disease severity and mortality through a systematic review and meta-analysis.

METHODS: We searched PubMed and CINAHL databases as well as pre-print servers for studies investigating usage of ACEIs/ARBs in patients with COVID-19 compared to a control group of COVID-19 patients without ACEI/ARB use. COVID-19 related severity of disease, and death were identified as end points. Pooled odds ratios (OR) and their 95% confidence intervals (CI) were calculated using random-effects model.

RESULTS: 21 studies were included in the meta-analysis. For mortality with ACEI/ARB use, the pooled odds ratio was 1.29 [0.89-1.87] p = 0.18 with heterogeneity of 91%, while the pooled OR for COVID-19 severity was 0.94 [0.59-1.50] p = 0.81 with heterogeneity of 89% (Figure 2). In combining both mortality and severe disease outcomes, the pooled odds ratio was 1.09 [0.80-1.48] p = 0.58 but with heterogeneity of 92%.

EXPERT OPINION: Even on pooled analysis of both un-adjusted data, adjusted data(studies with matched controls) and taking into account factors such as risk of bias of studies via meta regression and sensitivity analyses, the results hold true that ACEI/ARB use is not associated with COVID-19 disease severity or mortality. To look for any potential beneficial effects, randomized controlled trials are needed.

CONCLUSION: use of ACEI/ARB was not associated with increased mortality or severe COVID-19.

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

Family Medicine (FM)/General Practice (GP) rater

This is an important study, and is of importance to primary care practitioners because of the many patients taking Ace inhibitors who may be concerned about reports of COVID associated problems.

Hospital Doctor/Hospitalists rater

This is relevant and current. This is now already known, but it's good to have more definitive evidence, as it has been a subject of controversy earlier.

Infectious Disease rater

This is more reassuring data that ACEIs & ARBs are not harmful for patients with COVID.

Infectious Disease rater

This meta analysis confirms that ACE Inhibitors and ARBs do not increase mortality or disease severity in COVID infection.

Intensivist/Critical Care rater

The article provides an important background on the role of ACE2 receptors in the pathophysiology of SARS-Cov19 infection. The aim of the study is to assess the severity and mortality from SARS-CoV19 in patients using ACEI/ARB, compared with patients infected without using the medicines. The systematic review; although limited by the scarcity of studies, concluded that there were no statistically significant differences for severity and mortality between groups. The authors were thorough in controlling confounders and heterogeneity between groups.

Respirology/Pulmonology rater

Useful systematic review on an interesting current clinical question.