An updated meta-analysis: The effect of angiotensin-converting enzyme inhibitors and angiotensin receptor blockers in the mortality of hypertensive patients with confirmed COVID-19 infection

Abstract

Abstract Funding Acknowledgements Type of funding sources: None. Background One of the most common co-morbidities identified among COVID-19 patients was hypertension. Debates on use of Angiotensin-Converting Enzyme Inhibitors (ACEI) and Angiotensin-Receptor blockers (ARB) emerged due to an interaction of the said drugs with Angiotensin-converting enzyme 2 (ACE2), an enzyme which is a point of entry of coronavirus. This study aims to give an update on the work of Zhang et al13 in exploring the association of ACEI/ARB use on mortality and disease severity. Methods This meta-analysis involves review of observational studies among hypertensive COVID-19 patients with composite data on ACEI and ARB use. The literature search included studies published from December 2019 until June 30, 2020. Analyses were performed determining the odds ratio of each event using the raw data obtained from each study. Random effects model and Cochran-Mantel-Haenszel Method were utilized at 95% confidence interval. To check for heterogeneity, X2 test and I2 statistic were calculated. Subgroup analyses on ACEI users and ARB users were also done. Cochrane Review Manager (REVMAN 5.3) was used and Forest plots were generated. In this update, the total population of patients with confirmed COVID-19 infection was more than 50,000 with hypertensive patients comprising more than half of the sample population. The analyses done manifested decreased frequency of both outcomes with ACEI/ARB use. Results The calculated odds ratio for mortality and disease severity were 0.63 and 0.56, respectively. However, a statistically significant heterogeneity existed for both outcomes. Subgroup analyses among ACEI users versus ACEI/ARB non-users (odds ratio for mortality = 0.95, I2 = 0%; and odds ratio for disease severity = 0.30, I2 = 0%), and ARB users versus ACEI/ARB non-users (odds ratio for mortality = 0.70, I2 =f 68%; and odds ratio for disease severity = 0.48, I2 = 77%) also manifested decreased frequency of both outcomes. However, significant heterogeneity exists among the ARB users, which is in contrary among the ACEI users. Conclusion The use of ACEI contributes to a statistically significant reduction of mortality and disease severity among hypertensive patients with confirmed COVID-19 infection. We recommend continuing analysis of association of ACEI and ARB use and clinical outcomes since recent analysis suggests a beneficial effect especially in the ACEI group. At present, our findings are still in line with the current recommendation to not discontinue the use of ACEI and ARB among our hypertensive patients.