Effects of Renin-Angiotensin system blockers on outcomes from COVID-19: A systematic review and meta-analysis of randomised controlled trials

Eur Heart J Cardiovasc Pharmacother. 2023 Sep 22:pvad067. doi: 10.1093/ehjcvp/pvad067. Online ahead of print.


Background and aims: Randomised controlled trials (RCTs) have assessed the effects of renin-angiotensin system (RAS) blockers in adults with COVID-19. This meta-analysis provides estimates of the safety and efficacy of treatment with (versus without) RAS blockers from these trials.

Methods: PubMed, Web of Science, and ClinicalTrials.gov were searched (March 1-April 12, 2023). Event/patient numbers were extracted, comparing ACE inhibitor/ARB treatment, to no treatment, for the outcomes: intensive care unit (ICU) admission, mechanical ventilation, vasopressor use, acute kidney injury (AKI), renal replacement therapy (RRT), acute myocardial infarction, stroke/transient ischaemic attack, heart failure, thromboembolic events, and all-cause death. Fixed-effects meta-analysis estimates were pooled.

Results: Sixteen RCTs including 3492 patients were analysed. Compared with discontinuation of RAS blockers, continuation was not associated with increased risk of ICU (RR 0.96, 0.66-1.41), ventilation (RR 0.77, 0.55-1.09), vasopressors (RR 0.92, 0.58-1.44), AKI (RR 1.01, 0.40-2.56), RRT (RR 1.01, 0.46-2.21), or thromboembolic events (RR 1.07, 0.36-3.19). RAS blocker initiation was not associated with increased risk of ICU (RR 0.71, 0.47-1.08), ventilation (RR 1.12, 0.91-1.38), AKI (RR 1.28, 0.89-1.86), RRT (RR 1.66, 0.89-3.12), or thromboembolic events (RR 1.20, 0.06-23.70), although vasopressor use increased (RR 1.27, 1.02-1.57). The RR for all-cause death in the continuation/discontinuation trials was 1.24 (0.80-1.92), and 1.22 (0.96-1.55) in the initiation trials. In patients with severe/critical COVID-19, RAS blocker initiation increased the risk of all-cause death (RR 1.31, 1.01-1.72).

Conclusion: ACE inhibitors and ARBs may be continued in non-severe COVID-19 infection, where indicated. Conversely, initiation of RAS blockers may be harmful in critically ill patients. PROSPERO registration number: CRD42023408926.

Keywords: Angiotensin receptor blocker; Angiotensin-converting enzyme inhibitor; COVID-19; Meta-analysis; Randomised controlled trial; Renin-angiotensin system; Severe acute respiratory syndrome coronavirus 2.