The Association of Withdrawing Maintenance Renin-Angiotensin System Inhibitor on All-Cause Mortality and Intensive Care Unit Admission Among Hypertensive Patients Admitted for Mild to Moderate COVID-19 infection:A Meta-analysis of Observational Studies

Abstract

INTRODUCTION: The pandemic caused by coronavirus disease 2019 (COVID-19) posed a serious challenge to all health care systems in the world. It has been found to be harmful in people with underlying cardiovascular diseases, particularly in patients with systemic hypertension, which may be due to upregulation of angiotensin-converting enzyme 2 (ACE2) expression, which may lead to increased severe acute respiratory syndrome coronavirus 2 virulence. Renin-angiotensin system inhibitor (RASI) acts by blocking the angiotensin-converting enzyme and angiotensin II type 1 receptors, which in turn affects the production of the ACE2 protein. Hence, there have been arguments on whether to continue or discontinue this medication. Given the widespread use of RASIs globally and the fact that they are generally cardioprotective, research into the safety of continuing these maintenance medications in patients hospitalized with mild to moderate COVID-19 is immensely needed. METHODS: This meta-analysis involved review of observational studies among hypertensive patients on maintenance ACE inhibitor or angiotensin-receptor blocker with confirmed mild to moderate COVID-19 infection. Analyses were performed to determine the adjusted hazard 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, χ2 test and I2 statistic were calculated. Cochrane ReviewManager (RevMan version 5.3) was used for data analysis, and forest plots were generated. RESULTS: At 95% confidence interval, the adjusted hazard ratios for all-cause mortality and intensive care unit (ICU) admission at 95% confidence interval were 1.64 (1.22, 2.21) and 1.93 (1.34, 2.79), respectively. The tests of overall estimate effect for both outcomes were P < 0.0001 for all-cause mortality and P = 0.0003 for ICU admission. CONCLUSION: Discontinuation of maintenance RASI during hospitalization is associated with increased all-cause mortality and ICU admission among hypertensive patients with mild to moderate COVID-19 infection. KEYWORDS: angiotensin-converting enzyme inhibitors, angiotensin-receptor blockers, coronavirus, COVID-19, renin-angiotensin system inhibitor