COVID-19 Evidence Alerts
from McMaster PLUSTM

Current best evidence for clinical care (more info)

Etiology Barochiner J, Martinez R Use of inhibitors of the renin-angiotensin system in hypertensive patients and COVID-19 severity: A systematic review and meta-analysis. J Clin Pharm Ther. 2020 Aug 7. doi: 10.1111/jcpt.13246.

WHAT IS KNOWN AND OBJECTIVE: Controversy has arisen in the scientific community on whether the use of renin-angiotensin system (RAS) inhibitors in the context of COVID-19 would be beneficial or harmful. A meta-analysis of eligible studies comparing the occurrence of severe and fatal COVID-19 in infected hypertensive patients who were under treatment with angiotensin-converting enzyme inhibitors (ACEI) or angiotensin receptor blockers (ARB) vs no treatment or other antihypertensives was conducted.

METHODS: PubMed, Google Scholar, the Cochrane Library, medRxiv and bioRxiv were searched for relevant studies. Fixed-effects models or random-effects models were used depending on the heterogeneity between estimates.

RESULTS AND DISCUSSION: A total of eighteen studies with 17 311 patients were included. The use of RAS inhibitors was associated with a significant 16% decreased risk of the composite outcome (death, admission to intensive care unit, mechanical ventilation requirement or progression to severe or critical pneumonia): RR: 0.84 (95% CI: 0.73-0.95), P = .007, I2  = 65%.

WHAT IS NEW AND CONCLUSION: The results of this pooled analysis suggest that the use of ACEI/ARB does not worsen the prognosis of COVID-19, and could even be protective in hypertensive subjects. Hypertensive patients should continue these drugs even if they become infected with SARS-CoV-2.

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

Infectious Disease rater

This meta analysis adds to similar literature showing that there is little to no effect of drugs directed at the renin-angiotensin-aldosterone (RAAS) system on the course of COVID-19 disease. The international Society of Hypertension, European Society of Cardiology, and the American College of Cardiology, among others have all agreed that there is no modificiation of RAAS therapy needed in the setting of COVID-19.

Intensivist/Critical Care rater

I am not a fan of meta-analyses mainly because most of them are not good and are attempts after the fact to fix issues with data. Having said that, the message in this paper is probably important because of the retracted paper by Desai et al.

Internal Medicine rater

These are common drugs and the question is continually asked.

Respirology/Pulmonology rater

Meta-analysis with moderate-to-high heterogeneity (addressed through random-effects modeling) that well describes the limitations in regard to where the data they used came from (in reference to the quality of the included studies).

Respirology/Pulmonology rater

Meta-analysis of observational studies that found ACE or ARB use was associated with a slightly decreased risk for severe adverse outcomes of COVID-19. 1/3 of included studies were preprints, but results were similar when these were excluded. Nearly all the studies were small and under-powered, so the meta-analysis adds new information. A limitation is the high degree of statistical heterogeneity, which was unexplored but may result from pooling studies looking at different outcomes into a single composite (this seems unorthodox). There is also evidence of publication bias. Nevertheless, the pooled evidence seems sufficient to provide reassurance that continuing ACE inhibitors or ARBs will not increase risk for adverse outcomes in patients who develop COVID-19.