Journal Article Argues for Continued ARB Use, Despite COVID-19 Concerns

As pharmacists likely are well aware, social media is filled with warnings that patients taking renin-angiotensin system blockers, especially angiotensin II type 1 receptor blockers, are at greater risk from COVID-19. Find out why an article in an American Heart Association journal strongly urges that patients continue to use those drugs and argues that the greater danger, without more evidence, is in discontinuing the therapy.

MIAMI – With some reports – and social media chatter -- suggesting that patients should stop taking renin-angiotensin system (RAS) blockers, particularly angiotensin II type 1 receptor blockers (ARBs), because they might be more susceptible to bad outcomes from the novel coronavirus virus, experts are warning against discontinuing the drugs. .

Writing in the journal Hypertension, authors from the University of Miami, Northwestern university and Erasmus Medical Centre in the Netherlands caution that there is little credible or consistent evidence to back up those concerns. The authors further emphasize that stopping the medication could dramatically increase health risks for hundreds of millions of patients with hypertension, congestive heart failure, and chronic kidney disease.

"The only thing we can conclude definitively, based on all the known data, is that there is no credible evidence whatsoever that ARBs enhance susceptibility to COVID," said co-author Murray Epstein, MD, emeritus professor of medicine at the University of Miami Miller School of Medicine who edits the only medical textbook that focuses exclusively on ARBs.

The article notes, “During the spread of the severe acute respiratory syndrome coronavirus-2, some reports of data still emerging and in need of full analysis indicate that certain groups of patients are at risk of COVID-19. This includes patients with hypertension, heart disease, diabetes mellitus, and clearly the elderly.”

The authors point out that many of those patients are treated with renin-angiotensin system blockers, adding, “Because the ACE2 (angiotensin-converting enzyme 2) protein is the receptor that facilitates coronavirus entry into cells, the notion has been popularized that treatment with renin-angiotensin system blockers might increase the risk of developing a severe and fatal severe acute respiratory syndrome coronavirus-2 infection.:

Their article discusses the concept, explaining, “ACE2 in its full-length form is a membrane-bound enzyme, whereas its shorter (soluble) form circulates in blood at very low levels. As a mono-carboxypeptidase, ACE2 contributes to the degradation of several substrates including angiotensins I and II. ACE (angiotensin-converting enzyme) inhibitors do not inhibit ACE2 because ACE and ACE2 are different enzymes. Although angiotensin II type 1 receptor blockers have been shown to upregulate ACE2 in experimental animals, the evidence is not always consistent and differs among the diverse angiotensin II type 1 receptor blockers and differing organs.”

The authors further emphasize that “there are no data to support the notion that ACE inhibitor or angiotensin II type 1 receptor blocker administration facilitates coronavirus entry by increasing ACE2 expression in either animals or humans.”

In fact, they cite animal studies that support the opposite concept – that elevated ACE2 expression confers potential protective pulmonary and cardiovascular effects.

“In summary, based on the currently available evidence, treatment with renin-angiotensin system blockers should not be discontinued because of concerns with coronavirus infection,” the article concludes.

"People are making an unadvised leap," Epstein asserts. "The logic goes that, if it enhances penetrability, it enhances susceptibility to the disease, but that's a dangerous conclusion. What investigators have found varies widely, depending on the organ studied, the experimental animal model and the ARB being used in the study. In summary, there is a complete lack of consistency."

Maintaining there is no credible evidence that ARBs increase COVID-19 risk, Epstein points to the documented dangers for patients who stop taking their medications. "This would be a double tragedy, because it would be happening precisely at a time when our hospital and ICU resources are stressed to the limit," he said. "It will further tax our medical facilities and hospitals, and it will be truly tragic."

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