Relation Between Renin–Angiotensin–Aldosterone System Inhibitors and COVID-19 Severity

ABSTRACT

Background: Angiotensin-converting enzyme 2 (ACE2) receptor serves as a receptor for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the virus causing COVID-19, to enter the lungs. Angiotensin-converting enzyme inhibitors (ACEIs) and angiotensin receptor blockers (ARBs) may increase the expression of ACE2, resulting in concerns that patients with COVID-19 who are receiving these agents may be at increased risk of severe disease. This study was conducted to further investigate the effects of ACEIs and ARBs on the severity of COVID-19 in hospitalized hypertensive patients. Methods: The study was a retrospective observational study. The medical records of all adult hypertensive patients who were hospitalized at Dammam Medical Complex (DMC) between March 1, 2020, and December 31, 2020, due to COVID-19 were reviewed. The hypertensive patients who were receiving ACEIs or ARBs were compared with the other hypertensive patients who were not on ACEIs or ARBs. Results: A total of 148 hypertensive patients were included in the analysis. They consisted of 106 male and 42 female patients (72% and 28%, respectively). Nearly half of the patients were Saudi (75 patients, 50%). A total of 81 patients were in the ACEI/ARB group, and 67 patients were in the control group. There were no differences between the two groups in age, diabetic status, history of chronic kidney disease, initial blood pressure measurements, and initial oxygen requirements, but the control group contained fewer female patients (18% versus 37%) and Saudi patients (36% versus 63%) than the ACEI/ARB group (p-values = 0.017 and 0.002, respectively). The use of ACEIs or ARBs was associated with significant reductions in ICU admission (9% versus 31%, p-value = 0.001), need for intubation (7% versus 28%, p-value = 0.002), and death (2% versus 24%, p-value = 0.000). A significant negative association between the use ACEIs or ARBs and mortality was also observed in the multivariate analysis after the adjustment for the possible confounders, with an odds ratio (OR) of 0.087 and a 95% confidence interval (CI) of 0.017-0.449. Conclusions: ACEIs and ARBs have no adverse effects on the clinical prognosis of COVID-19 patients with hypertension. Their use might be even beneficial and protective, but future larger studies are needed to confirm these effects. In the meanwhile, they should be continued in COVID-19 hypertensive patients unless their use is contraindicated for other reasons (e.g., hypotension, hyperkalemia, or acute kidney injury (AKI)).