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An umbrella review and meta-analysis of the use of renin-angiotensin system drugs and COVID-19 outcomes: what do we know so far?
  • Amanj Kurdi,
  • Natalie Weir ,
  • Tanja Mueller
Amanj Kurdi
University of Strathclyde

Corresponding Author:amanj.baker@strath.ac.uk

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Natalie Weir
Strathclyde Institute of Pharmacy and Biomedical Sciences
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Tanja Mueller
Strathclyde Institute of Pharmacy and Biomedical Sciences
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Aim To provide a comprehensive assessment of the effect of angiotensin-converting enzyme inhibitors (ACEIs) and angiotensin receptor II blockers (ARBs) on COVID-19 related outcomes by summarising the currently available evidence. Methods This was an umbrella review of systematic reviews/meta-analysis conducted using Medline (OVID), Embase, Scopus, Cochrane library and medRxiv from inception to 1st February 2021. Systematic reviews with meta-analysis that evaluated the effect of ACEIs/ARBs on COVID-19 related clinical outcomes were eligible. Studies’ quality was appraised using the AMSTAR 2 Critical Appraisal Tool. Data were analysed using the random-effects modelling including several sub-group analyses. Heterogenicity was assessed using I2 statistic. The study protocol was registered in PROSPERO (CRD42021233398). Results Overall, 47 reviews were eligible for inclusion. Out of the nine COVID-19 outcomes evaluated, there was significant associations between ACEIs/ARBs use and each of death (OR=0.80, 95%CI=0.75-0.86; I2=51.9%), death/ICU admission as composite outcome (OR=0.86, 95%CI=0.80-0.92; I2=43.9%), severe COVID-19 (OR=0.86, 95%CI=0.78-0.95; I2=68%), and hospitalisation (OR=1.23, 95%CI=1.04-1.46; I2= 76.4%). The significant reduction in death/ICU admission, however, was higher among studies which presented adjusted measure of effects (OR=0.63, 95%CI=0.47-0.84) and were of moderate quality (OR=0.74, 95%CI=0.63-0.85). There was no evidence of any significant association between ACEIs, or ARBs and COVID-19 outcomes. Conclusions Collective evidence from observational studies indicate a good quality evidence on the significant association between ACEIs/ARBs use and reduction in death and death/ICU admission, but poor-quality evidence on both reducing severe COVID-19 and increasing hospitalisation. Our findings further support the current recommendations of not discontinuing ACEIs/ARBs therapy in patients with COVID-19.