An umbrella review and meta-analysis of the use of renin-angiotensin
system drugs and COVID-19 outcomes: what do we know so far?
Abstract
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.