Estimation of Renin-Angiotensin-Aldosterone-System (RAAS)-Inhibitor effect on COVID-19 outcome: A Meta-analysis

Abstract

Background and rationale: Some studies of hospitalized patients suggested that the risk of death and/or severe illness due to COVID-19 is not associated with the use of angiotensin-converting enzyme inhibitors (ACEIs) and/or angiotensin II receptor type 1 blockers (ARBs). Nevertheless, some controversy still exists and there is limited information of the ACEIs/ARBs effect size on COVID-19 prognosis.

Aim and methods: We aimed to measure the effect of ACEIs and/or ARBs on COVID-19 severe clinical illness by a meta-analysis. Literature search included all studies published since the COVID-19 outbreak began (December 2019) until May 9, 2020. We analyzed information from studies that included tested COVID-19 patients with arterial hypertension as comorbidity prior to hospital admission and history of taking ACEIs, ARBs, or ACEIs/ARBs.

Results: We included 16 studies that involved 24,676 COVID-19 patients, and we compared patients with critical (n = 4134) vs. non-critical (n = 20,542) outcomes. The overall assessment by estimating random effects shows that the use of ACEIs/ARBs is not associated with higher risk of in-hospital-death and/or severe illness among hypertensive patients with COVID-19 infection. On the contrary, effect estimate shows an overall protective effect of RAAS inhibitors/blockers (ACEIs, ARBs, and/or ACEIs/ARBs) with ∼ 23 % reduced risk of death and/or critical disease (OR: 0.768, 95%CI: 0.651-0.907, p=0.0018). The use of ACEIs (OR:0.652, 95%CI:0.478-0.891, p=0.0072) but not ACEIs/ARBs (OR:0.867, 95%CI:0.638-1.179, p =NS) or ARBs alone (OR:0.810, 95%CI:0.629-1.044, p=NS) may explain the overall protection displayed by RAAS intervention combined.

Conclusion: RAAS inhibitors might be associated with better COVID-19 prognosis.

Keywords: Angiotensin II receptor type 1 blockers; Angiotensin II-converting enzyme inhibitors; COVID-19; RAAS inhibitors; cardiovascular disease; diabetes; hypertension; prognosis.

Graphical abstract

Figure 1

Quantitative estimation of the effect of angiotensin-converting enzyme inhibitors (ACEIs) or angiotensin II receptor type 1 blockers (ARBs), alone or undistinct drug (ACEIs/ARBs) on COVID-19 severe clinical illness. Association analysis of death/critical illness vs. non-critical illness in COVID-19 patients receiving ACEIs, ARBs, or ACEIs/ARBs without discrimination. For the dichotomous variable (critical / non‐critical), the effect denotes odds ratio (OR) and corresponding 95% confidence interval (CI). Because of the presence of heterogeneity, a random effect model was adopted to estimate the pooled ORs. This model assumes that the treatment effect is not the same across all studies included in the analysis. The first author of the study is shown under the sub‐heading “study name.” Popul: indicates the use of ACEIs, ACEIs/ARBs, or ARBs. In the graph, the filled squares denote the effect of individual studies, and filled diamonds express combined fixed and random effects.

Figure 2

Quantitative estimation of the effect of angiotensin-converting enzyme inhibitors (ACEIs) or angiotensin II receptor type 1 blockers (ARBs), alone or undistinct drug (ACEIs/ARBs) on COVID-19 severe clinical illness after removing the indicated study at a time. The first author of the removed study is shown under the sub‐heading “study name.” Popul: indicates the use of ACEIs, ACEIs/ARBs, or ARBs.