A systematic review and meta-analysis of the use of renin-angiotensin
system drugs and COVID-19 clinical outcomes: What is the evidence so
far?
Abstract
Aim To provide a comprehensive/updated evaluation of the effect of
ACEIs/ARBs on COVID-19 related-clinical outcomes, including exploration
of inter-class differences between ACEIs and ARBs. Methods This was a
systematic review/meta-analysis conducted in Medline (OVID), Embase,
Scopus, Cochrane library and medRxiv from inception to 22nd May-2020.
English studies that evaluated the effect of ACEIs/ARBs among patients
with COVID-19 were included. The study outcomes included any COVID-19
related-clinical outcomes. Studies’ quality was appraised using the
Newcastle-Ottawa Scale. Data were analysed using the random-effects
modelling stratified by ACEIs/ARBs, ACEIs, and ARBs. Heterogenicity was
assessed using I2 statistic. Several sub-group analyses were conducted
to explore the impact of potential confounders. Results Out of the
identified 452 studies, 27 studies were eligible for inclusion. The
pooled analyses showed non-significant associations between ACEIs/ARBs
and death (OR:0.97, 95%CI:0.75,1.27), ICU admission
(OR:1.09;95%CI:0.65,1.81), death/ICU admission (OR:0.67;
95%CI:0.52,0.86), risk of COVID-19 infection (OR:1.01;
95%CI:0.93,1.10), severe infection (OR:0.78; 95%CI:0.53,1.15) and
hospitalisation (OR:1.15; 95%CI:0.81,1.65). However, the sub-group
analyses indicated different results such as significant association
between ACEIs/ARBs and hospitalisation among USA studies (OR:1.59;
95%CI:1.03,2.44), peer-reviewed (OR:1.93, 95%CI:1.38,2.71), good
quality and studies which reported adjusted measure of effect (OR:1.30,
95%CI:1.10,1.50). Significant differences were found between ACEIs and
ARBs with the latter being significantly associated with lower risk of
acquiring COVID-19 infection (OR:0.24; 95%CI: 0.17,0.34). Conclusions
High-quality evidence exist for the effect of ACEIs/ARBs on some
COVID-19 clinical outcomes. For the first time, we provided evidence,
albeit of low quality, on inter-class differences between ACEIs and ARBs
for some of the reported clinical outcome.