Mortality and Disease Severity Among COVID-19 Patients Receiving Renin-Angiotensin System Inhibitors: A Systematic Review and Meta-analysis

Am J Cardiovasc Drugs. 2020 Dec;20(6):571-590. doi: 10.1007/s40256-020-00439-5. Epub 2020 Sep 12.

Abstract

Introduction: The use of renin-angiotensin system (RAS) inhibitors, including angiotensin-converting enzyme inhibitors (ACEIs) and angiotensin receptor blockers (ARBs), was alleged to cause a more severe course of novel coronavirus disease 2019 (COVID-19).

Methods: We systematically reviewed the published studies to assess the association of RAS inhibitors with mortality as well as disease severity in COVID-19 patients. A systematic literature search was performed to retrieve relevant original studies investigating mortality and severity (severe/critical disease) in COVID-19 patients with and without exposure to RAS inhibitors.

Results: A total of 59 original studies were included for qualitative synthesis. Twenty-four studies that reported adjusted effect sizes (24 studies reported mortality outcomes and 16 studies reported disease severity outcomes), conducted in RAS inhibitor-exposed and unexposed groups, were pooled in random-effects models to estimate overall risk. Quality assessment of studies revealed that most of the studies included were of fair quality. The use of an ACEI/ARB in COVID-19 patients was significantly associated with lower odds (odds ratio [OR] = 0.73, 95% confidence interval [CI] 0.56-0.95; n = 18,749) or hazard (hazard ratio [HR] = 0.75, 95% CI 0.60-0.95; n = 26,598) of mortality compared with non-use of ACEI/ARB. However, the use of an ACEI/ARB was non-significantly associated with lower odds (OR = 0.91, 95% CI 0.75-1.10; n = 7446) or hazard (HR = 0.73, 95% CI 0.33-1.66; n = 6325) of developing severe/critical disease compared with non-use of an ACEI/ARB.

Discussion: Since there was no increased risk of harm, the use of RAS inhibitors for hypertension and other established clinical indications can be maintained in COVID-19 patients.

Publication types

  • Meta-Analysis
  • Systematic Review

MeSH terms

  • Angiotensin Receptor Antagonists / therapeutic use*
  • Angiotensin-Converting Enzyme Inhibitors / therapeutic use*
  • COVID-19 / mortality*
  • Humans
  • Hypertension / drug therapy*
  • Observational Studies as Topic
  • Renin-Angiotensin System / drug effects
  • SARS-CoV-2
  • Severity of Illness Index

Substances

  • Angiotensin Receptor Antagonists
  • Angiotensin-Converting Enzyme Inhibitors