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?

Conflicting evidence exists about the effect of angiotensin‐converting enzyme inhibitors (ACEIs)/angiotensin receptor blockers (ARBs) on COVID‐19 clinical outcomes. We aimed to provide a comprehensive/updated evaluation of the effect of ACEIs/ARBs on COVID‐19‐related clinical outcomes, including exploration of interclass differences between ACEIs and ARBs, using a systematic review/meta‐analysis approach conducted in Medline (OVID), Embase, Scopus, Cochrane library, and medRxiv from inception to 22 May 2020. English studies that evaluated the effect of ACEIs/ARBs among patients with COVID‐19 were included. Studies’ quality was appraised using the Newcastle‐Ottawa Scale. Data were analyzed using the random‐effects modeling stratified by exposure (ACEIs/ARBs, ACEIs, and ARBs). Heterogeneiity was assessed using I(2) statistic. Several subgroup analyses were conducted to explore the impact of potential confounders. Overall, 27 studies were eligible. The pooled analyses showed nonsignificant 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 hospitalization (OR:1.15; 95%CI:0.81,1.65). However, the subgroup analyses indicated significant association between ACEIs/ARBs and hospitalization 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). In conclusion, high‐quality evidence exists for the effect of ACEIs/ARBs on some COVID‐19 clinical outcomes. For the first time, we provided evidence, albeit of low quality, on interclass differences between ACEIs and ARBs for some of the reported clinical outcomes.