Impact of in-hospital discontinuation with angiotensin receptor blockers or converting enzyme inhibitors on mortality of COVID-19 patients: a retrospective cohort study
Authors: de Abajo Francisco J. , Rodríguez-Miguel Antonio , Rodríguez-Martín Sara , Lerma Victoria , García-Lledó Alberto ,   on behalf of MED-ACE2-COVID19 Study Group, de Abajo F. J. , Rodríguez-Miguel A. , Rodríguez-Martín S. , Lerma V. , García-Lledó A. , Barreira-Hernández D. , Rodríguez-Puyol D. , Laosa O. , Pedraza L. , Rodríguez-Mañas L. , Aguilar M. , de Pablo I. , Gálvez M. A. , García-Luque A. , Puerro M. , Aparicio R. M. , García-Rosado V. , Gutiérrez-Ortega C. , Laredo L. , González-Rojano E. , Pérez C. , Ascaso A. , Elvira C. , Mejía-Abril G. , Zubiaur P. , Santos-Molina E. , Pintos-Sánchez E. , Navares-Gómez M. , Abad-Santos F. , Centeno G. A. , Sancho-Lopez A. , Payares-Herrera C. , Diago-Sempere E. 
Published: May 2021

Abstract
Background
In the first wave of the COVID-19 pandemic, the hypothesis that angiotensin receptor blockers (ARBs) and angiotensin-converting enzyme inhibitors (ACEIs) increased the risk and/or severity of the disease was widely spread. Consequently, in many hospitals, these drugs were discontinued as a “precautionary measure”. We aimed to assess whether the in-hospital discontinuation of ARBs or ACEIs, in real-life conditions, was associated with a reduced risk of death as compared to their continuation and also to compare head-to-head the continuation of ARBs with the continuation of ACEIs.

Methods
Adult patients with a PCR-confirmed diagnosis of COVID-19 requiring admission during March 2020 were consecutively selected from 7 hospitals in Madrid, Spain. Among them, we identified outpatient users of ACEIs/ARBs and divided them in two cohorts depending on treatment discontinuation/continuation at admission. Then, they were followed-up until discharge or in-hospital death. An intention-to-treat survival analysis was carried out and hazard ratios (HRs), and their 95%CIs were computed through a Cox regression model adjusted for propensity scores of discontinuation and controlled by potential mediators.

Results
Out of 625 ACEI/ARB users, 340 (54.4%) discontinued treatment. The in-hospital mortality rates were 27.6% and 27.7% in discontinuation and continuation cohorts, respectively (HR=1.01; 95%CI 0.70–1.46). No difference in mortality was observed between ARB and ACEI discontinuation (28.6% vs. 27.1%, respectively), while a significantly lower mortality rate was found among patients who continued with ARBs (20.8%, N=125) as compared to those who continued with ACEIs (33.1%, N=136; p=0.03). The head-to-head comparison (ARB vs. ACEI continuation) yielded an adjusted HR of 0.52 (95%CI 0.29–0.93), being especially notorious among males (HR=0.34; 95%CI 0.12–0.93), subjects older than 74 years (HR=0.46; 95%CI 0.25–0.85), and patients with obesity (HR=0.22; 95%CI 0.05–0.94), diabetes (HR=0.36; 95%CI 0.13–0.97), and heart failure (HR=0.12; 95%CI 0.03–0.97).

Conclusions
The discontinuation of ACEIs/ARBs at admission did not improve the in-hospital survival. On the contrary, the continuation with ARBs was associated with a trend to a reduced mortality as compared to their discontinuation and to a significantly lower mortality risk as compared to the continuation with ACEIs, particularly in high-risk patients.