Figuring out whether the drugs increase susceptibility to the coronavirus or increase the likelihood of developing more severe disease is particularly important because the medications are so widely used. ACE inhibitors and ARBs are frequently prescribed for patients with hypertension, heart failure, ischemic heart disease, and diabetes.
A significant number of patients who develop the disease take ACE inhibitors or ARBs. That’s led some researchers to suggest that the drugs could increase the expression of angiotensin-converting enzyme 2 (ACE2) in humans, as they do in mice, noted a Viewpoint article in JAMA Cardiology on April 3 by an international team of scientists led by Chirag Bavishi, MD, MPH, of the Warren Alpert Medical School of Brown University and the Lifespan Cardiovascular Institute in Providence, Rhode Island.
Increased ACE2 expression could be bad news, as the novel coronavirus accesses target cells through the ACE2 receptor. Potentially, increased ACE2 expression could put individuals at greater risk of infection.
Other researchers have suggested that COVID-19 binding to ACE2 could throw off the ACE/ACE2 balance in the body, causing constriction of the blood vessels in the lung and increasing organ damage, leading to greater risk of acute lung injury.
Alternatively, increasing the levels of ACE2 in the bloodstream could block COVID-19 from entering some cells, reducing the risk of lung injury, a benefit also seen in studies with mice, the Viewpoint authors say.
With so much controversy surrounding the drugs and COVID-19, the American Heart Association, American College of Cardiology, and the Heart Failure Society of America issued a joint statement on March 17. They noted that currently “there are no experimental or clinical data demonstrating beneficial or adverse outcomes with background use of ACE inhibitors, ARBs or other RAAS antagonists in COVID-19 or among COVID-19 patients with a history of cardiovascular disease treated with such agents.”
Consequently, the groups recommended continuation of the medications as prescribed and adjustment in patients who develop COVID-19 based on the individual’s hemodynamic status and clinical presentation, until additional studies provide more definitive evidence. “Therefore, be advised not to add or remove any RAAS-related treatments, beyond actions based on standard clinical practice,” they conclude.
Researchers who authored a review in the New England Journal of Medicine on March 30 went further. They “explicitly raise[d] the concern that withdrawal of RAAS inhibitors may be harmful in certain high-risk patients with known or suspected COVID-19.”
Specifically, they noted that heart failure may be present in more than 40% of critically ill COVID-19 patients in the United States and that previous studies have shown that withdrawing RAAS inhibitors in this patient group results in significant decline in clinical status. Further, patients prescribed RAAS inhibitors following a myocardial infarction have lower early mortality that those who are not. Growing awareness of the cardiac involvement in many patients with COVID-19 increases the concern that discontinuing RAAS inhibitors in coronavirus patients could increase cardiovascular risk.
So, for now, encourage your patients to stay on their ARBs and ACE inhibitors until they have a chance to discuss any change with their healthcare provider.
