RAAS inhibitors for hypertensive patients during Covid-19 infection – a metanalysis

Abstract

Inhibition of the Renin Angiotensin Aldosterone system (RAAS) is the leading form of anti-hypertensive treatment, through blockade of the angiotensin-converting enzyme 2 receptor (ACE2-r) by angiotensin enzyme inhibitors (ACE-is) and angiotensin receptor blockers (ARBs). However, the ACE-r has been found to be a functional receptor for the viral entry of SARS-CoV-2, and increased upregulation of ACE2 by inhibitors could increase the severity of infection. Previous to the SARS-CoV-2 outbreak, typical practice in patients with risk of infection would be to withhold ACE inhibitors due to evidence of renal failure. This thesis reviews the impact of RAAS inhibitor use in COVID-19 patients, and if withholding ACE inhibitors could affect the clinical outcome of patients. A total of 22 studies were located form database searching (PubMed, MedRxiv, Google scholar), 15,784 hypertensive COVID-19 patients were documented, with 8,035 taking ACE-is/ARBs treatment in comparison to 7,024 without. RAAS inhibitors were found to decrease likelihood of mortality (OR 0.68 [0.51, 0.90], p = 0.008), but there was no statistically significant difference between RAAS and Non-RAAS in severity (OR 0.91 [0.63, 1.31], p= 0.62). Following these results there would not be sufficient evidence to remove longstanding RAAS inhibitor medication in COVID-19 patients. Rapid data collected during observational trials can now be utilised in long term randomised controlled studies currently ongoing, such as BRACE-CORONA. This allows the opportunity for further analyses of the association between the RAAS system, new variants, genetic polymorphism and the maintenance of blood pressure.