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 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.