COVID-19 Evidence Alerts
from McMaster PLUSTM

Current best evidence for clinical care (more info)

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Etiology Patoulias D, Katsimardou A, Stavropoulos K, et al. Renin-Angiotensin System Inhibitors and COVID-19: a Systematic Review and Meta-Analysis. Evidence for Significant Geographical Disparities. Curr Hypertens Rep. 2020 Sep 10;22(11):90. doi: 10.1007/s11906-020-01101-w.

PURPOSE OF REVIEW: While the COVID-19 pandemic is constantly evolving, it remains unclear whether the use of angiotensin-converting enzyme (ACE) inhibitors or angiotensin receptor blockers (ARBs) affects the clinical course of SARS-CoV-2 infection. For this meta-analysis, PubMed, CENTRAL, and grey literature were searched from their inception to 19 May 2020 for randomized, controlled trials or observational studies that evaluate the association between the use of either ACE inhibitors or ARBs and the risk for major clinical endpoints (infection, hospitalization, admission to ICU, death) in adult patients during the COVID-19 pandemic. In addition, a subgroup geographical analysis of outcomes was performed. Studies including less than 100 subjects were excluded from our analysis.

RECENT FINDINGS: In total, 25 observational studies were included. ACE inhibitors and ARBs were not associated with increased odds for SARS-CoV-2 infection, admission to hospital, severe or critical illness, admission to ICU, and SARS-CoV-2-related death. In Asian countries, the use of ACE inhibitors/ARBs decreased the odds for severe or critical illness and death (OR = 0.37, 95% CI 0.16-0.89, I2 = 83%, and OR = 0.62, 95% CI 0.39-0.99, I2 = 0%, respectively), whereas they increased the odds for ICU admission in North America and death in Europe (OR = 1.75, 95% CI 1.37-2.23, I2 = 0%, and OR = 1.68, 95% CI 1.05-2.70, I2 = 82%, respectively). ACE inhibitors might be marginally protective regarding SARS-CoV-2-related death compared with ARBs (OR = 0.86, 95% CI 0.74-1.00, I2 = 0%). Randomized controlled trials are needed to confirm the aforementioned associations between ACE inhibitors, ARBs, and SARS-CoV-2.

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

Cardiology rater

The more we learn, the more it appears we don't know. Genetics/geographics are clearly highly relevant. How these data compare with current situation (this data is from early 2020) with virus having mutated slightly becoming more infectious but also more vulnerable will have to be shown. For now, I think we still are none the wiser but perhaps the evidence swung slightly towards 'avoid ACE/ARB in Europe/North America'.

Intensivist/Critical Care rater

Strengths: • Good intention of performing meta-analysis on debatable topic which made a sensation. Weaknesses: • As like any such meta-analysis, it has risk of selection and exclusion bias. • Several key aspects of impact of ACEI/ARB on heart and lung damage in SARS-COV-2 have not been assessed or searched for. It is important to note that ACEI/ARB have mostly protective effect on lung and heart and the preventive or damaging role of them in SARS-COV-2 should have been looked than only seeing ICU mortality, hospital admission. • Hardly any explanation is given why the results differed from earlier assumption, difference in regional variation and racial variation in relation to their outcomes when difference was found in subgroup analysis. Overall, this is average general quality meta-analysis which served to clear some points on this controversial debate. However, nothing much is mentioned about the reason why the outcome differed even in main and subgroup analysis.