Effect of Discontinuing vs Continuing Angiotensin-Converting Enzyme Inhibitors and Angiotensin II Receptor Blockers on Days Alive and Out of the Hospital in Patients Admitted With COVID-19

Lópes, Renato D.; Macedo, Ariane Vieira Scarlatelli; Silva, Pedro Gabriel Melo de Barros e; Moll-Bernardes, Renata; Santos, Tiago Mendonça dos; Mazza, Lilian; Feldman, André; Arruda, Guilherme D’Andréa Saba; Albuquerque, Denílson Campos de; Camiletti, Angelina; Sousa, Andréa Silvestre de; Paula, Thiago Ceccatto de; Giusti, Karla G. D.; Domiciano, Rafael A. M.; Noya-Rabelo, Márcia; Hamilton, Alan M.; Loures, Vitor Alves; Dionísio, Rodrigo M.; Furquim, Thyago Antônio Biagioni; Luca, Fabio A De; Sousa, Ítalo Bruno dos Santos; Bandeira, Bruno Santana; Zukowski, Cleverson; Oliveira, Ricardo; Ribeiro, Noara Barros; Moraes, Jeffer L. de; Petriz, João Luiz Fernandes; Pimentel, Adriana M.; Miranda, Jacqueline S.; Abufaiad, Bárbara Elaine de Jesus; Gibson, C. Michael; Granger, Christopher B.; Alexander, John H.; Souza, Olga Ferreira de

doi:10.1001/jama.2020.25864

Cited by 333 publications

(361 citation statements)

References 43 publications

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“…Recently, the results from two randomized clinical trials in which regular users of RASIs who were admitted to hospital for COVID-19 were assigned to discontinuation or continuation arms, have been reported (BRACE-CORONA [18] and REPLACE COVID [19] trials) and both found no difference in the mortality rates, supporting our results.…”

Section: Discussionsupporting

confidence: 88%

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

Rodríguez‐Miguel

Rodríguez‐Martín

et al. 2021

Preprint

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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

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Section: Discussionsupporting

confidence: 88%

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

Rodríguez‐Miguel

Rodríguez‐Martín

et al. 2021

Preprint

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“…While most studies have reported no association between the use of ACEI or ARB and the occurrence of COVID-19 [16][17][18][19][20][21][22][23][24][25], we found that the presence of a claim record of an ACEI prescription was associated with an 8% reduction in the OR of a COVID-19 infection. While this finding warrants further investigation, we do not believe it justifies a change in clinical practice.…”

Section: Plos Onecontrasting

confidence: 82%

“…patients in France [21], 1,603 patients in Italy [22], 338 patients in Saudi Arabia [23], 659 patients in Brazil [24], and 1,449 patients in the US [25] revealed no significant associations. Our study design allowed us to differentiate ACEI use from ARB use by utilizing claims data from Veterans with prescriptions for ACEI only, for ARB only, or for either ACEI or ARB, compared to Veterans with prescriptions for neither ACEI nor ARB.…”

Section: Plos Onementioning

confidence: 88%

The association of COVID-19 occurrence and severity with the use of angiotensin converting enzyme inhibitors or angiotensin-II receptor blockers in patients with hypertension

Wang

Ndiwane³

et al. 2021

PLoS ONE

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Background A number of studies have reported the association between the use of angiotensin-converting enzyme inhibitor (ACEI) and angiotensin-II receptor blocker (ARB) medications and the occurrence or severity of coronavirus disease 2019 (COVID-19). Published results are inconclusive, possibly due to differences in participant comorbidities and sociodemographic backgrounds. Since ACEI and ARB are frequently used anti-hypertension medications, we aim to determine whether the use of ACEI and ARB is associated with the occurrence and severity of COVID-19 in a large study of US Veterans with hypertension. Methods Data were collected from the Department of Veterans Affairs (VA) National Corporate Data Warehouse (VA-COVID-19 Shared Data Resource) between February 28, 2020 and August 18, 2020. Using data from 228,722 Veterans with a history of hypertension who received COVID-19 testing at the VA, we investigated whether the use of ACEI or ARB over the two years prior to the index date was associated with increased odds of (1) a positive COVID-19 test, and (2) a severe outcome (hospitalization, mortality, and use of intensive care unit (ICU) and/or mechanical ventilation) among COVID-19-positive patients. We used logistic regression with and without propensity score weighting (PSW) to estimate the odds ratio (OR) and 95% confidence interval (95% CI) for the association between ACEI/ARB use and a positive COVID-19 test result. The association between medication use and COVID-19 outcome severity was examined using multinomial logistic regression comparing participants who were not hospitalized to participants who were hospitalized, were admitted to the ICU, used a mechanical ventilator, or died. All models were adjusted for relevant covariates, including demographics (age, sex, race, ethnicity), selected comorbidities, and the Charlson Comorbidity Index (CCI). Results The use of ACEI significantly decreased the odds of a positive COVID-19 test among Veterans with hypertension (OR = 0.917, (0.887, 0.948) and OR = 0.926, (0.894, 0.958) with PSW). The use of ACEI, but not of ARB, was also associated with significantly increased odds of using mechanical ventilators (OR = 1.265, (1.010, 1.584) and OR = 1.210, (1.053, 1.39) with PSW) among all COVID-19 inpatients compared to outpatients. Conclusions In this study of Veterans with hypertension, ACEI was significantly associated with decreased odds of testing positive for COVID-19. With the exception of the association of ACEI with a small non-clinically-important increase in the odds of using mechanical ventilators, neither ACEI nor ARB was found to be associated with clinical severity or mortality among COVID-19-positive Veterans. The results of this study need further corroboration and validation in other cohort samples outside the VA.

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“…Исследование REPLACE COVID проводилось в 20 крупных больницах в семи странах мира с участием 152 пациентов (средний возраст 62 года), которые перед госпитализацией с COVID-19 получали ИАПФ или БРА II [60]. В группах больных, рандомизированных для продолжения (n = 75) или прекращения приема ИАПФ или БРА II (n = 77) не наблюдалось существенных различий среднего глобального рейтинга (первичная конечная точкавремя до наступления смерти, продолжительность искусственной вентиляции легких, время на заместительной почечной терапии или вазопрессорной терапии, а также полиорганной дисфункции в период госпитализации) -73 против 81 соответственно.…”

Section: применение блокаторов раас при известном или предполагаемом Covid-19unclassified

Treatment of hypertension during the COVID-19 pandemic: questions about the blockade of the renin-angiotensin-aldosterone system

Kanorskiy

2021

Medicinskij sovet

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Arterial hypertension was one of the most common comorbidities associated with a high risk of death in hospitalized patients with COVID-19. Patients with hypertension are routinely and according to standards treated with angiotensinconverting enzyme inhibitors (ACE inhibitors) or angiotensin receptor blockers (ARB) II. ACE inhibitors or ARB II are included in fixed combinations of antihypertensive drugs recommended for patients with uncomplicated hypertension, as well as when combined with various comorbidities. During the COVID-19 pandemic, there were suggestions about the potential for a negative effect of drugs of these classes on the course and outcomes of a new coronavirus infection. There was a need for a quick response from the most reputable medical organizations to the question of the use of ACE inhibitors and ARB II during the COVID-19 pandemic. The expert position was soon published despite the lack of evidence from randomized clinical trials. Was there any reason for concern about the treatment of ACE inhibitors and ARB II for COVID-19? What are the relationships between the renin-angiotensin-aldosterone system (RAAS) and COVID-19? Is there any new data from clinical trials that can confirm or deny the previously presented position of professional societies regarding the use of RAAS blockers in COVID-19? What is the role of the difference in the mechanism of action of an ACE inhibitor and ARB II in COVID-19? Is it possible that RAAS blockers will be helpful in treating COVID-19? Will the tactics of hypertension pharmacotherapy change in the near future? In this review article, modern concepts on this problem are discussed and answers to the listed questions reflecting the achieved level of knowledge are formulated.

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Effect of Discontinuing vs Continuing Angiotensin-Converting Enzyme Inhibitors and Angiotensin II Receptor Blockers on Days Alive and Out of the Hospital in Patients Admitted With COVID-19

Cited by 333 publications

References 43 publications

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

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

The association of COVID-19 occurrence and severity with the use of angiotensin converting enzyme inhibitors or angiotensin-II receptor blockers in patients with hypertension

Treatment of hypertension during the COVID-19 pandemic: questions about the blockade of the renin-angiotensin-aldosterone system

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