Raas inhibition, mortality, and severity in COVID-19 patients: A systematic review and meta-analysis

ABSTRACT

Background: The effect of angiotensin-receptor blockers (ARBs) and angiotensinconverting enzyme inhibitors (ACEi) on outcome and severity in COVID-19 patients has been postulated. Methods: We performed a systematic review in different databases to identify studies and research work that assessed the association of ACEi/ARBs on the severity of illness and mortality in COVID-19 subjects. Inclusion criteria for our meta-analysis were all studies that included human subjects with COVID-19 infection, reported mortality and severity of the disease, and described ACEi/ARB treatment. The data collected were the name of the first author, journal title, the country of the study, sample size, relative risk and confidence intervals for association of ACEi/ARB treatment and mortality and severity. We used the random-effects model for the meta-analysis and the funnel plot analysis to assess potential publication bias. Results: Out of 4,702 records reviewed in different databases, 11 papers were included in our meta-analysis. Altogether, 8,643 patients were included in the final analysis. Random effects model (REM) for the relationship between ACEi/ARB and survival showed that ACEi/ARB does not affect survival (relative risk [RR]=0.81, confidence interval ranges [CIR] from 0.53 to 1.23). There was no evidence of heterogeneity with I-squared =25.5% and p<0.235. By applying Egger's test, there was no evidence of small studies effect with P=0.64. REM for the relationship between ACEi/ARB and disease severity showed that ACEi/ARB are not related to disease severity (RR=0.90, CIR from 0.70 to 1.15). There was evidence of heterogeneity with I-squared =56.2% and p=0.01. By applying Egger's test, there was no evidence of small studies effect with P=0.93. Conclusions: Based on the results of this meta-analysis, ACEi/ARB are not associated with increased mortality or severity in COVID-19 subjects.