An umbrella review and meta‐analysis of renin–angiotensin system drugs use and COVID‐19 outcomes

BACKGROUND: Despite the availability of extensive literature on the effect of angiotensin‐converting enzyme inhibitors (ACEIs)/angiotensin‐receptor blockers (ARBs) on COVID‐19 outcomes, the evidence is still controversial. We aimed to provide a comprehensive assessment of the effect of ACEIs/ARBs on COVID‐19‐related outcomes by summarising the currently available evidence. METHODS: An umbrella review was conducted using Medline (OVID), Embase, Scopus, Cochrane library and medRxiv from inception to 1 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 subgroup analyses. Heterogenicity was assessed using I(2) statistic. The study protocol was registered in PROSPERO (CRD42021233398) and reported using PRISMA guidelines. 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; 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). 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.