Three Studies Find No Harm from ACE Inhibitors or ARBs in COVID-19

By Amy Orciari Herman

Edited by Susan Sadoughi, MD, and André Sofair, MD, MPH

Use of angiotensin-converting-enzyme (ACE) inhibitors or angiotensin-receptor blockers (ARBs) is not associated with poor outcomes in patients with novel coronavirus disease (COVID-19), according to three observational studies in the New England Journal of Medicine.

In the first, researchers used an international registry to study nearly 9000 patients in 11 countries who were hospitalized with COVID-19 between December 2019 and March 2020. Roughly 6% died in the hospital. After multivariable adjustment, the following were independent predictors of in-hospital death: age over 65, coronary artery disease, congestive heart failure, arrhythmia, chronic obstructive pulmonary disease, and current smoking. Use of ACE inhibitors or ARBs at admission was not associated with increased mortality risk; rather, evidence suggested ACE inhibitors were associated with decreased risk.

Next, researchers in Italy matched roughly 6300 patients with confirmed COVID-19 to 31,000 population-based controls. Using healthcare databases, they found that cases were more likely than controls to have received ACE inhibitors (24% vs. 21%) or ARBs (22% vs. 19%) in 2019. However, after multivariable adjustment, neither drug class was significantly associated with risk for mild-to-moderate or severe COVID-19.

And finally, researchers studied nearly 13,000 patients who underwent COVID-19 testing at a New York City health system; 47% had a positive result, of whom 17% had severe illness. After propensity-score matching for receipt of five classes of antihypertensive drugs, no class — including ACE inhibitors or ARBs — was associated with increased risk for COVID-19 or severe disease.

Editorialists write, "Each of these studies has weaknesses inherent in observational data, but we find it reassuring that three studies in different populations and with different designs arrive at the consistent message that the continued use of ACE inhibitors and ARBs is unlikely to be harmful in patients with COVID-19."