Angiotensin-converting enzyme (ACE) inhibitors and angiotensin receptor blockers (ARBs) are safe for use in patients with COVID-19, according to a study presented Tuesday at the European Society of Cardiology (ESC) 2020 virtual congress.
Renato D. Lopes, MD, PhD, of Duke Clinical Research Institute, presented the results on behalf of the BRACE CORONA investigators as a Hot Line trial at ESC.
Membrane-bound ACE2 is the receptor protein that allows entry of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) into the cells of infected patients, leading to COVID-19.
BRACE CORONA sought to address two conflicting hypotheses about the use of ACE inhibitors/ARBs in COVID-19. The first hypothesis theorized that ACE inhibitors and ARBs could increase ACE2 receptor expression and, thus, enhance viral binding and viral entry, leading to worse outcomes. The alternative hypothesis was based on the idea that by decreasing production of angiotensin II with an ACE inhibitor or ARB, the generation of angiotensin (1–7) is enhanced, which may attenuate inflammation and fibrosis and, therefore, could decrease the severity of lung injury.
To test these hypotheses, the investigators designed a phase IV, multicenter, randomized clinical trial that enrolled 659 patients chronically on ACE inhibitors or ARBs who were hospitalized with a confirmed diagnosis of COVID-19. Patients were randomized in a 1:1 fashion to continue on their current ACE inhibitor/ARB regimen or suspend treatment of ACE inhibitors/ARBs for 30 days. After randomization, the investigators examined the number of days alive and out of hospital at 30 days. Patients who were using more than three antihypertensive drugs, sacubitril/valsartan, or who were hemodynamically unstable at presentation were excluded from the study.
The results showed that there was no difference in the number of days alive or the number of days out of hospital in each group.
In discussing the results, Lopes said, “This is the first randomized data assessing the role of continuing versus stopping ACE inhibitors and ARBs in patients with COVID-19.”
He went on to say that, “In patients hospitalized with COVID-19, suspending ACE inhibitors and ARBs for 30 days did not impact the number of days alive and out of hospital.”
“Because these data indicate that there is no clinical benefit from routinely interrupting these medications in hospitalized patients with mild to moderate COVID-19, they should generally be continued for those with an indication,” Lopes concluded.
The BRACE CORONA trial was sponsored by the D'Or Institute for Research and Education and the Brazilian Clinical Research Institute.