Safety of ACEi and ARB in COVID-19 management: A retrospective analysis

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV2)is a highly contagious virus that has infected 260 million individuals since December 2019. The severity of coronavirus disease 2019 (COVID-19) depends upon the complex interplay between viral factors and the host's inflammatory response, which can trigger a cascadeeventually leading to multiorgan failure. There is contradictory evidence that angiotensin-converting enzyme (ACEi) or angiotensin receptor blockers (ARBs) may affect mortality in patients with severe COVID-19, theoretically due to interaction with the bradykinin pathway. Therefore, we aim to explore the association between ACEi and ARB use and mortality in severe SARS-CoV2 infection.Severe acute respiratory yndrome with coronavirus (SARS-CoV2) is a highly contagious virus that has infected 260 million individuals since December 2019. The severity of COVID-19 depends upon the complex interplay between viral factors and the host's inflammatory response, which can trigger a cascadeeventually leading to multiorgan failure. There is contradictory evidence that angiotensin-converting enzyme (ACEi) or angiotensin receptor blockers (ARBs) may affect mortality in patients with severe COVID-19, theoretically due to interaction with the bradykinin pathway. Therefore, we aim to explore the association between ACEi and ARB use and mortality in severe SARS-CoV2 infection.

This multicenter retrospective observational study enrolled 2935 COVID-19 patients admitted at six hospitals in Southern California, USA, between March 2020 and August 2021. Our primary outcome was the association of pre-hospital use of ACEi and ARB on in-hospital mortality in COVID-19 patients. First, relevant deidentified patient data were extracted using an SQL program from the electronic medical record. Then, a bivariate analysis of the relationship between ACEi and ARB use and different study variables using χ² and t test was done. Finally, we did a backward selection Cox multivariate regression analysis using mortality as a dependent variable.

Of the 2935 patients in the study, hypertension was present in 40.6%, and congestive heart failure in 13.8%. ACEi and ARB were used by 17.5% and 11.3% of patients, respectively, with 28.8% of patients on either medication. After adjusting for confounding variables in the multivariate analysis, the use of ACEi (HR: 1.226, 95% CI: 0.989-1.520) or ARB (HR: 0.923, 95% CI: 0.701-1.216) was not independently associated with increased mortality.

Our results are consistent with the clinical guidelines and position statements per the International Society of Hypertension, that there is no indication to stop the use of ACEi/ARB in COVID-19 patients.