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

Backgrounds Evidence from several meta-analyses are still controversial about the effects of angiotensin-converting enzyme inhibitors (ACEIs)/angiotensin-receptor blockers (ARBs) on COVID-19 outcomes. Purpose Umbrella review of systematic reviews/meta-analysis to provide comprehensive assessment of the effect of ACEIs/ARBs on COVID-19 related outcomes by summarising the currently available evidence. Data Source Medline (OVID), Embase, Scopus, Cochrane library and medRxiv from inception to 1 st February 2021. Study Selection Systematic reviews with meta-analysis that evaluated the effect of ACEIs/ARBs on COVID-19 related clinical outcomes Data Extraction Two reviewers independently extracted the data and assessed studies’ risk of bias using AMSTAR 2 Critical Appraisal Tool. Data Synthesis Pooled estimates were combined using the random-effects meta-analyses model including several sub-group analyses. 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; I 2 =51.9%), death/ICU admission as composite outcome (OR=0.86, 95%CI=0.80-0.92; I 2 =43.9%), severe COVID-19 (OR=0.86, 95%CI=0.78-0.95; I 2 =68%), and hospitalisation (OR=1.23, 95%CI=1.04-1.46; I 2 = 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). Limitations The effect of unmeasured confounding could not be ruled out. Only 21.3% (n=10) of the studies were of ‘moderate’ quality. Conclusion 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. Registration The study protocol was registered in PROSPERO (CRD42021233398). Funding Source None