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; Abdulaziz S Almulhim; Ahmed A Alrashed; Ivo Abraham

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

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

Authors

Ahmad A Alamer^{1

2}, Abdulaziz S Almulhim³, Ahmed A Alrashed⁴, Ivo Abraham^{1

5}

Affiliations

¹ Center for Health Outcomes and PharmacoEconomic Research, University of Arizona, 1295 N Martin Ave, Tucson, AZ 85721, USA.
² Department of Clinical Pharmacy, College of Pharmacy, Prince Sattam Bin Abdulaziz University, Alkharj 11942, Saudi Arabia.
³ Department of Pharmacy Practice, College of Clinical Pharmacy, King Faisal University, Al-Ahasa 31982, Saudi Arabia.
⁴ Pharmaceutical Service Department, Main Hospital, King Fahad Medical City, Riyadh 11564, Saudi Arabia.
⁵ Department of Pharmacy Practice and Science, College of Pharmacy, University of Arizona, Tucson, AZ 85721, USA.

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 (OR_p) 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 OR_p = 1.28 [95% CI = 1.04; 1.56] and a decrease in China with OR_p = 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.