ACE Inhibitors, ARBs Do Not Worsen COVID-19 Risk

The use of angiotensin-converting enzyme inhibitors (ACEIs) or angiotensin-receptor blockers (ARBs) does not appear to worsen the severity of cases of coronavirus disease 2019 (COVID-19), according to new research.

The study, published in the journal Annals of Internal Medicine, also found that there is likely no connection between such medications and the chance of a symptomatic patient testing positive for SARS-CoV-2. The results refute concerns by some that these medications might make patients more vulnerable amid the COVID-19 pandemic.

Corresponding author Devan Kansagara, MD, MCR, of the Veterans Health Administration’s Portland Health Care System, explained in the study that early evidence from China showing hypertension and diabetes were common among patients with COVID-19, and that patients with those pre-existing conditions were experiencing more severe cases, led some experts to hypothesize that the 2 types of therapies might in some way be making people more susceptible to the disease.

“The proposed mechanism by which ACEIs and ARBs may play a role in COVID-19 is through upregulation of the angiotensin enzyme 2 (ACE2), which is presumed to act as a functional receptor for SARS-CoV-2 to gain entry to host cells,” Kansagara and colleagues wrote.

Still, they noted that investigators have not yet been able to consistently demonstrate such an upregulation. Furthermore, others have hypothesized that the drugs might actually help patients fight off the virus.

In an attempt to get to the bottom of the question, the investigators pulled together existing literature from medical databases, including ClinicalTrials.gov, that involved patients taking ACEIs or ARBs and SARS-CoV-2 infection rates or COVID-19 disease severity and mortality. The study is being structured as a living systematic review, with plans to continue ongoing surveillance for a year.

Though about half of the studies were small and did not adjust for confounding variables, Kansagara and colleagues found consistent outcomes in the research. Two retrospective studies showed use of the therapies was not connected with a higher risk of a positive SARS-CoV-2 test result, and a third case-control study found no link between the drugs and COVID-19 illness.

Beyond that, the investigators located 14 observational studies, with more than 23,000 enrollees, that consistently failed to show a link between disease severity and the 2 medications.

The group also found 4 registered randomized trials that are designed not to gauge ACEIs and ARBs as potential exacerbating factors in COVID-19, but rather to test them as possible therapies for the disease.

Altogether, the Kansagara and colleagues said they have high certaining that the drugs are not associated with more severe disease, and moderate certainty that the drugs aren’t associated with higher rates of positive SARS-CoV-2 tests in symptomatic patients.

“On the basis of the findings from this rapidly expanding literature, no indication exists to prophylactically stop ACEI or ARB treatment because of concerns about COVID-19,” investigators concluded. “Indeed, the withdrawal of long-term ACEIs or ARBs may be harmful, especially in patients with heart failure, because observational studies and trials have suggested that discontinuation of ACEI or ARB therapy is associated with worse outcomes.

Kansagara and colleagues noted in their discussion that the COVID-19 research landscape is rapidly changing, but they said they will continue to consult databases and add to their findings as more research is completed and published.