Continuing versus suspending angiotensin-converting enzyme inhibitors and angiotensin receptor blockers: Impact on adverse outcomes in hospitalized patients with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)--The BRACE CORONA Trial

Abstract

Background Angiotensin-converting enzyme-2 (ACE2) expression may increase due to upregulation in patients using angiotensin-converting enzyme inhibitors (ACEI) and angiotensin receptor blockers (ARBs). Because renin-angiotensin system blockers increase levels of ACE2, a protein that facilitates coronavirus entry into cells, there is concern that these drugs could increase the risk of developing a severe and fatal form of COVID-19. The impact of discontinuing ACEI and ARBs in patients with COVID-19 remains uncertain. Design BRACE CORONA is a pragmatic, multicenter, randomized, phase IV, clinical trial that aims to enroll around 500 participants at 34 sites in Brazil. Participants will be identified from an ongoing national registry of suspected and confirmed cases of COVID-19. Eligible patients using renin-angiotensin system blockers (ACEI/ARBs) with a confirmed diagnosis of COVID-19 will be randomized to a strategy of continued ACEI/ARB treatment versus temporary discontinuation for 30 days. The primary outcome is the median days alive and out of the hospital at 30 days. Secondary outcomes include progression of COVID-19 disease, all-cause mortality, death from cardiovascular causes, myocardial infarction, stroke, transient ischemic attack, new or worsening heart failure, myocarditis, pericarditis, arrhythmias, thromboembolic events, hypertensive crisis, respiratory failure, hemodynamic decompensation, sepsis, renal failure, and troponin, B-type natriuretic peptide (BNP), Nterminal-proBNP, and D-dimer levels. Summary BRACE CORONA will evaluate whether the strategy of continued ACEI/ARB therapy compared with temporary discontinuation of these drugs impacts clinical outcomes among patients with COVID-19.

Use of distinct anti‐hypertensive drugs and risk for COVID‐19 among hypertensive people: A population‐based cohort study in Southern Catalonia, Spain

“…Concerns have been raised about the possible association between the use of RAAS inhibitors (mainly ACEIs and/or ARBs) with the risk of SARS‐CoV‐2 infection, the risk of severe COVID‐19 among those infected, or the risk of in‐hospital death among those with a positive test 4,5,6 . Several studies have concluded that there is no evidence of poor outcomes (increased severity or in‐hospital death) in patients infected with SARS‐CoV‐2 taking RAAS inhibitors 8,9,10 .…”

“…Considering hypertension, which is the most common comorbidity in middle‐aged and older adults (who suffer the greatest burden of fatal COVID‐19 cases), a possible beneficial/harm effect using some first‐line anti‐hypertensive medications such as angiotensin‐converting enzyme inhibitors (ACEIs) and/or angiotensin II receptor blockers (ARBs) has become controversial for the management of hypertensive patients in the current COVID‐19 pandemic period 4,5,6 …”

“…Since ACE2 was identified as functional receptors to SARS‐CoV‐2, 7 it has been speculated that renin‐angiotensin‐aldosterone system (RAAS) inhibition could increase ACE2 expression and, thus, ACEIs/ARBs might be harmful in patients with COVID‐19 4,5,6 . However, most recent publications have not found evidence of harm with the continued use of RAAS inhibitors 8,9,10 .…”

Gastrointestinal Manifestations and Associated Health Outcomes of COVID-19: A Brazilian Experience From the Largest South American Public Hospital

“…Our study reported that chronic use of ACE-I/ARB is a protective factor for mechanical ventilation and associated with a lower mortality. A Randomized Clinical Trial comparing suspending or continuing use of ACE-I/ARB in chronic users is currently under way and should aid in understanding the role of those drugs among COVID-19 patients ( 21 ).…”

Cardiovascular disease and the impact of COVID‐19

“…infection; yet there is lack of robust evidence supporting the use or discontinuation of RAAS medications. 2,3 Although, there is a theory that ACEi/ARBs antagonise RAAS which might reduce inflammation in COVID-19 pneumonia, thus reducing mortality. 2,4 The study by Zhang et al 4 reports the conclusion of a lower risk of all-cause mortality in the ACEi/ARBs group compared with the nonusers for hypertension.…”