Renin-Angiotensin-Aldosterone System Inhibitor Withdrawal During COVID-19 Hospitalization Increases Mortality Risk

Senior woman wearing mask infected by coronavirus on hospital bed receiving medicine by drip. Close-up fingers of the senior patient ´s hand while she is sleeping. Horizontal photo
Researchers assessed whether discontinuing treatment with angiotensin-converting enzyme inhibitors, aldosterone-receptor blockers, and mineralocorticoid receptor antagonists during COVID-19 hospitalization increases the risk of mortality.

Discontinuation of mineralocorticoid receptor antagonists (MRA) or angiotensin-converting enzyme ACE inhibitors at hospital admission was associated with an increased risk of mortality in patients with COVID-19 infection. These findings were published in Revista Portuguesa de Cardiologia.

Patients (N=2042) hospitalized with COVID-19 infection at the Hospital Universitario La Paz in Spain between March and April 2020 were included in this observational cohort study. The researchers assessed the risk of all-cause mortality among patients who discontinued treatment with renin-angiotensin-aldosterone system (RAAS) inhibitors following hospitalization for COVID-19 infection. Cox proportional hazards regression was used to adjust for patient factors, including age, sex, cardiovascular risk factors, baseline comorbidities, and in-hospital treatments.

The study population comprised patients with a mean age of 68.4±17.6 years, 57.1% were men, and 53% had hypertension. There were 847 patients on RAAS inhibitors prior to hospital admission. Of these patients, 22.9%, 16.8%, and 4.1% were receiving treatment with ACE inhibitors, angiotensin-receptor blockers (ARB), and MRA, respectively. At hospital admission, RAAS inhibitor treatment was discontinued in 411 patients.

Among patients included in the analysis, 583 died within a median follow-up period of 57 days, with mortality rates increased among those who discontinued vs continued treatment with RAAS inhibitors following hospital admission (44.3% vs 28.7%; P <.001).

Results of a multivariable analysis with covariates adjusted via Cox hazards regression showed that an increased risk of mortality was independently associated with RAAS inhibitor withdrawal (hazard ratio [HR], 1.47; 95% CI, 1.15-1.89; P <.001).

Stratified by type of RAAS inhibitor treatment, an increased risk of mortality was independently associated with MRA (HR, 2.10; 95% CI, 1.32-3.34; P <.001) and ACE inhibitor (HR, 1.62; 95% CI, 1.23-2.14; P <.001) withdrawal, but the association was not statistically significant in regard to ARB withdrawal (HR, 1.25; 95% CI, 0.93-1.68; P =.140). The poorest prognoses were noted among patients who discontinued ACE inhibitors or ARB plus MRA at hospital admission (P <.001).

This study was potentially limited by its observational design and small sample size.

According to the researchers, “even though the underlying link between ACE inhibitors withdrawal and higher mortality is unknown, there is the possibility that it may be related to a strong inflammatory state in the patients discontinuing these drugs.”

Disclosure: Multiple authors declared affiliations with industry. Please see the original reference for a full list of disclosures.


Caro-Codón J, R JR, Iniesta AM, et al. Impact of renin-angiotensin-aldosterone inhibitors withdrawal on mortality in covid-19 patients. Rev Port Cardiol. Published online June 27, 2022. doi:10.1016/j.repc.2021.06.021