Renin-Angiotensin System Inhibitors in Patients With COVID-19: A Meta-Analysis of Randomized Controlled Trials Led by the International Society of Hypertension


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BACKGROUND: Published randomized controlled trials are underpowered for binary clinical end points to assess the safety and efficacy of renin-angiotensin system inhibitors (RASi) in adults with COVID-19. We therefore performed a meta-analysis to assess the safety and efficacy of RASi in adults with COVID-19. METHODS AND RESULTS: MEDLINE, EMBASE, Clini​calTr​, and the Cochrane Controlled Trial Register were searched for randomized controlled trials that randomly assigned patients with COVID-19 to RASi continuation/commencement versus no RASi therapy. The primary outcome was all-cause mortality at ≤30 days. A total of 14 randomized controlled trials met the inclusion criteria and enrolled 1838 participants (aged 59 years, 58% men, mean follow-up 26 days). Of the trials, 11 contributed data. We found no effect of RASi versus control on all-cause mortality (7.2% versus 7.5%; relative risk [RR], 0.95; [95% CI, 0.69–1.30]) either overall or in subgroups defined by COVID-19 severity or trial type. Network meta-analysis identified no difference between angiotensin-converting enzyme inhibitors versus angiotensin II receptor blockers. RASi users had a nonsignificant reduction in acute myocardial infarction (2.1% versus 3.6%; RR, 0.59; [95% CI, 0.33–1.06]), but increased risk of acute kidney injury (7.0% versus 3.6%; RR, 1.82; [95% CI, 1.05– 3.16]), in trials that initiated and continued RASi. There was no increase in need for dialysis or differences in congestive cardiac failure, cerebrovascular events, venous thromboembolism, hospitalization, intensive care admission, inotropes, or mechanical ventilation. CONCLUSIONS: This meta-analysis of randomized controlled trials evaluating angiotensin-converting enzyme inhibitors/angio-tensin II receptor blockers versus control in patients with COVID-19 found no difference in all-cause mortality, a borderline decrease in myocardial infarction, and an increased risk of acute kidney injury with RASi. Our findings provide strong evidence that RASi can be used safely in patients with COVID-19.

Original languageEnglish (US)
Article numbere026143
JournalJournal of the American Heart Association
Issue number17
StatePublished - Sep 6 2022

Bibliographical note

Funding Information:
Dr Gnanenthiran is supported by a postdoctoral fellowship from the Heart Foundation of Australia. Dr Chirinos has recently consulted for Bayer, Sanifit, Fukuda-Denshi, Bristol-Myers Squibb, JNJ, Edwards Life Sciences, Merck, NGM Biopharmaceuticals, and the Galway-Mayo Institute of Technology. He received University of Pennsylvania research grants from National Institutes of Health, Fukuda-Denshi, Bristol-Myers Squibb, Microsoft, and Abbott. He is named as inventor in a University of Pennsylvania patent for the use of inorganic nitrates/nitrites for the treatment of heart failure and preserved ejection fraction and for the use of biomarkers in heart failure with preserved ejection fraction. He has received payments for editorial roles from the American Heart Association, the American College of Cardiology, and Wiley. He has received research device loans from Atcor Medical, Fukuda-Denshi, Uscom, NDD Medical Technologies, Microsoft, and MicroVision Medical. Dr Schutte received consultancy fees from Abbott and speaker honoraria from Servier, Sanofi, Sun Pharmaceuticals, Omron, Takeda, and Novartis. Dr Stergiou received consultancy fees and speaker honoraria from Astra-Zeneca, Menarini, Novartis, Sanofi, and Servier. Dr Schlaich has received consulting fees and/or travel and research support from Medtronic, Abbott, Novartis, Servier, Pfizer, and Boehringer-Ingelheim. Dr Sharma reports receiving support from the Fonds de Recherche Santé Quebec Junior 1 clinician scholar program, Canada Institute for Health Research (grant 175095), Roche Diagnostics, Boeringer-Ingelheim, Novartis, and Takeda. Dr Poulter has received financial support from several pharmaceutical companies that manufacture blood pressure–lowering agents, for consultancy fees (Servier), research projects and staff (Servier, Pfizer), and for arranging and speaking at educational meetings (AstraZeneca, Lri Therapharma, Napi, Servier, Sanofi, Eva Pharma, Pfizer, Alkem Laboratories, and Glenmark Pharma). He holds no stocks or shares in any such companies. Dr Williams has received honoraria for lectures on hypertension from Servier, Menarini, Pfizer, Boehringer Ingelheim, and Daiichi Sankyo. The remaining authors have no disclosures to report.

Publisher Copyright:
© 2022 The Authors.


  • acute kidney injury
  • angiotensin II receptor blockers
  • angiotensin-converting enzyme inhibitors
  • COVID-19
  • hypertension
  • renin-angiotensin system inhibitors

PubMed: MeSH publication types

  • Journal Article
  • Meta-Analysis
  • Review


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