In-Hospital Continuation With Angiotensin Receptor Blockers Is Associated With a Lower Mortality Rate Than Continuation With Angiotensin Converting Enzyme Inhibitors in Covid-19 Patients: A Retrospective Cohort Study

Abstract

BackgroundSeveral studies have reported a reduced risk of death associated with the inpatient use of angiotensin receptor blockers (ARBs) and angiotensin converting enzyme inhibitors (ACEIs) in COVID-19 patients, but have been criticized for incurring in several types of bias. Also, most studies have pooled ACEIs and ARBs as if they were a unique group, overlooking their pharmacological differences. We aimed to assess whether the in-hospital continuation of ARBs and ACEIs, in regular users of these drugs, was associated with a reduced risk of death as compared to their discontinuation and also to compare head-to-head ARBs with ACEIs.MethodsAdult 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%CI were computed through a Cox regression model adjusted for propensity scores of discontinuation and controlled by potential mediators.ResultsOut 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).ConclusionsAmong regular users of ARBs admitted for COVID-19, the in-hospital continuation with them was associated with an improved survival, while this was not observed with ACEIs. Regular users of ARBs should continue with this treatment if admitted for COVID-19, unless medically contraindicated. In admitted ACEI users, a switching to ARBs should be considered, especially among high-risk patients.GRAPHICAL ABSTRACT

Real-world Evidence of Time-varying Effects of Renin-angiotensin System Inhibitors on Pneumonia and Related Deaths: A Territory-wide Cohort Study in 252,616 Patients With Diabetes (2002-2019)

“…There are few studies designed to compare use of ARBs-only with ACEi-only on pneumonia risk. In our direct comparison of ACEi-only and ARBs-only users who were well-matched for baseline characteristics, we found ARBs were superior to ACEi in reducing pneumonia events, which are consistent with some studies [25]. Both ARB and ACEi effectively block RAS, but only ARB selectively blocks the AT1-receptor and increases expression of ACE2 [26,27].…”

“…Given the high RAS activity in patients with diabetes, appropriate use of RASi is critical to protect the organs from the deleterious effects of Ang-II [25][26][27]. While both clinical trials and real-world evidence (RWE) had con rmed the bene ts of RASi on cardiovascular-renal outcomes [28,29], similar data on pneumonia as a major cause of morbidity and mortality in diabetes remain scarce.…”

“…While both clinical trials and real-world evidence (RWE) had con rmed the bene ts of RASi on cardiovascular-renal outcomes [28,29], similar data on pneumonia as a major cause of morbidity and mortality in diabetes remain scarce. The COVID-19 pandemic has led to the revisiting of the immunomodulating effects of RASi [25] with several researchers reporting reduced risk of pneumonia and in uenza-related death amongst patients treated with RASi [3,30,31]. There are a number of pharmacoepidemiological analyses exploring the RWE of RASi on pneumonia or pneumonia related deaths [3][4][5][6].…”

New Perspectives for Antihypertensive Sartans as Components of Co-crystals and Co-amorphous Solids with Improved Properties and Multipurpose Activity

“…Twenty two of these studies have already been completed. Some of the studies suggested reconsideration of ARBs in the treatment of COVID-19 patients and highlight the potential beneficial role of ARBs to improve the clinical outcomes of COVID-19 patients by controlling the RAAS (Renin-Angiotensin-Aldosterone System) dysfunction. , Other studies confirm safety of the ARBs treatment in COVID-19 patients − this type of uncertainty suggesting that ARBs may worsen the condition of patients with COVID-19 arose at the beginning of the pandemic and has been refuted. In addition to clinical trials, molecular docking studies have also been conducted to demonstrate the potential of ARBs to inhibit the COVID-19 main proteasethe best results were obtained for fimasartan and candesartan …”

Therapeutic Effectiveness and Safety of Repurposing Drugs for the Treatment of COVID-19: Position Standing in 2021

“…A recent preprint of a retrospective cohort study suggested higher survival rates for in-hospital high-risk COVID-19 patients with the use of ARBs than ACEIs ( de Abajo et al, 2021 ). Another retrospective cohort study in Wuhan suggested the beneficial role of ACEI/ARBs over calcium channel blockers in COVID-19 patients with hypertension ( Liu et al, 2021 ).…”