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. 2021 Jan 28;9(2):127.
doi: 10.3390/healthcare9020127.

Mortality, Severity, and Hospital Admission among COVID-19 Patients with ACEI/ARB Use: A Meta-Analysis Stratifying Countries Based on Response to the First Wave of the Pandemic

Ahmad A Alamer  1   2 , Abdulaziz S Almulhim  3 , Ahmed A Alrashed  4 , Ivo Abraham  1   5
Affiliations

Mortality, Severity, and Hospital Admission among COVID-19 Patients with ACEI/ARB Use: A Meta-Analysis Stratifying Countries Based on Response to the First Wave of the Pandemic

Ahmad A Alamer et al. Healthcare (Basel). .

Abstract

Background: The use of angiotensin-converting enzyme inhibitors (ACEIs) or angiotensin receptor blockers (ARBs) is controversial for treating COVID-19 patients. We aimed to estimate pooled risks of mortality, disease severity, and hospitalization associated with ACEI/ARB use and stratify them by country and country clusters.

Methods: We conducted a search in various databases through 4 July 2020 and then applied random-effects models to estimate pooled risks (ORp) across stratifications by country cluster. Clusters were chosen to reflect outbreak times (China followed by Korea/Italy, others subsequently) and mobility restrictions (China and Denmark/France/Spain with stricter lockdowns than the UK/US).

Results: Overall analysis showed no increase in mortality; however, a statistical increase in mortality was seen in the US/UK cluster with ORp = 1.28 [95% CI = 1.04; 1.56] and a decrease in China with ORp = 0.65 [95% CI = 0.43; 0.96] and France with OR = 0.31 [95% CI = 0.14; 0.69]. Severity and hospitalization were not statistically significant in the analysis; however, several associations were seen in specific countries but not in country clusters.

Conclusion: The country-cluster meta-analysis provided a reasonable explanation for COVID-19 mortality among ACEI/ARB users. The analysis did not explain differences in severity and suggested the involvement of other factors. Hospitalization findings among ACEI/ARB users may be considered informative as they may have been subjected to clinical decisions and hospital-bed availability.

Keywords: Covid-19; angiotensin II receptor blocker; angiotensin-converting enzyme inhibitor; disease severity; hospital admission; mortality.

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Conflict of interest statement

The authors have no financial or other beneficial interests related to the work reported herein to declare.

Figures

Figure 1
Figure 1
Forest plots for (A) mortality, (B) severity of COVID-19 disease, and (C) hospitalization. All studies were published in 2020. All citations included in the Supplementary Material Appendix to Table S1. The size of squares is proportional to the weight of each study. Horizontal lines indicate the 95% CI of each study; diamonds indicate the pooled estimate with 95% CI. Abbreviations: CI: confidence interval; OR: odds ratio. ACEI: Angiotensin-converting enzyme inhibitors. ARB: Angiotensin II receptor blockers.
Figure 1
Figure 1
Forest plots for (A) mortality, (B) severity of COVID-19 disease, and (C) hospitalization. All studies were published in 2020. All citations included in the Supplementary Material Appendix to Table S1. The size of squares is proportional to the weight of each study. Horizontal lines indicate the 95% CI of each study; diamonds indicate the pooled estimate with 95% CI. Abbreviations: CI: confidence interval; OR: odds ratio. ACEI: Angiotensin-converting enzyme inhibitors. ARB: Angiotensin II receptor blockers.
Figure 2
Figure 2
Forest plots for country clusters (A) mortality, (B) severity of COVID-19 disease, and (C) hospitalization. All studies were published in 2020. All citations included in the Supplementary Materials file Appendix to Table S1. The size of squares is proportional to the weight of each study. Horizontal lines indicate the 95% CI of each study; diamonds, the pooled estimate with 95% CI. Abbreviations: CI: confidence interval; OR: odds ratio. ACEI: Angiotensin-converting enzyme inhibitors. ARB: Angiotensin II receptor blockers.
Figure 2
Figure 2
Forest plots for country clusters (A) mortality, (B) severity of COVID-19 disease, and (C) hospitalization. All studies were published in 2020. All citations included in the Supplementary Materials file Appendix to Table S1. The size of squares is proportional to the weight of each study. Horizontal lines indicate the 95% CI of each study; diamonds, the pooled estimate with 95% CI. Abbreviations: CI: confidence interval; OR: odds ratio. ACEI: Angiotensin-converting enzyme inhibitors. ARB: Angiotensin II receptor blockers.
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