Controversy continued over the potential effect of drugs that interfere with the renin-angiotensin-aldosterone system via the angiotensin-converting enzymes (ACE) may have on exacerbating infection with the SARS-CoV-2 virus that causes COVID-19.
A joint statement from the American Heart Association, American College of Cardiology, and the Heart Failure Society of America on March 17 gave full, unqualified support to maintaining patients on drugs that work this way, specifically the ACE inhibitors and angiotensin-receptor blockers (ARBs), which together form a long-standing cornerstone of treatment for hypertension, heart failure, and ischemic heart disease.
The three societies “recommend continuation” of ACE inhibitors or ARBs “for all patients already prescribed.” The statement went on to say that patients already diagnosed with a COVID-19 infection “should be fully evaluated before adding or removing any treatments, and any changes to their treatment should be based on the latest scientific evidence and shared decision making with their physician and health care team.”
“We understand the concern – as it has become clear that people with cardiovascular disease are at much higher risk of serious complications including death from COVID-19. However, we have reviewed the latest research – the evidence does not confirm the need to discontinue ACE inhibitors or ARBs, and we strongly recommend all physicians to consider the individual needs of each patient before making any changes to ACE-inhibitor or ARB treatment regimens,” said Robert A. Harrington, MD, president of the American Heart Association and professor and chair of medicine at Stanford (Calif.) University, in the statement.
“There are no experimental or clinical data demonstrating beneficial or adverse outcomes among COVID-19 patients using ACE-inhibitor or ARB medications,” added Richard J. Kovacs, MD, president of the American College of Cardiology and professor of cardiology at Indiana University in Indianapolis.
The “latest research” referred to in the statement likely focuses on a report that had appeared less than a week earlier in a British journal that hypothesized a possible increase in the susceptibility of human epithelial cells of the lungs, intestine, kidneys, and blood vessels exposed to these or certain other drugs, like the thiazolidinedione oral diabetes drugs or ibuprofen, because they cause up-regulation of the ACE2 protein in cell membranes, and ACE2 is the primary cell-surface receptor that allows the SARS-CoV-2 virus to enter.
“We therefore hypothesize that diabetes and hypertension treatment with ACE2-stimulating drugs increases the risk of developing severe and fatal COVID-19,” wrote Michael Roth, MD, and his associates in their recent article (Lancet Resp Med. 2020 Mar 11. doi: 10.1016/S2213-2600[20]30116-8). While the potential clinical impact of an increase in the number of ACE2 molecules in a cell’s surface membrane remains uninvestigated, the risk this phenomenon poses should mean that patients taking these drugs should receive heightened monitoring for COVID-19 disease, suggested Dr. Roth, a professor of biomedicine who specializes in studying inflammatory lung diseases including asthma, and associates.
However, others who have considered the impact that ACE inhibitors and ARBs might have on ACE2 and COVID-19 infections have noted that the picture is not simple. “Higher ACE2 expression following chronically medicating SARS‐CoV‐2 infected patients with AT1R [angiotensin receptor 1] blockers, while seemingly paradoxical, may protect them against acute lung injury rather than putting them at higher risk to develop SARS. This may be accounted for by two complementary mechanisms: blocking the excessive angiotensin‐mediated AT1R activation caused by the viral infection, as well as up-regulating ACE2, thereby reducing angiotensin production by ACE and increasing the production” of a vasodilating form of angiotensin, wrote David Gurwitz, PhD, in a recently published editorial (Drug Dev Res. 2020 Mar 4. doi: 10.1002/ddr.21656). A data-mining approach may allow researchers to determine whether patients who received drugs that interfere with angiotensin 1 function prior to being diagnosed with a COVID-19 infection had a better disease outcome, suggested Dr. Gurwitz, a molecular geneticist at Tel Aviv University in Jerusalem.
The statement from the three U.S. cardiology societies came a few days following a similar statement of support for ongoing use of ACE inhibitors and ARBs from the European Society of Cardiology’s Council on Hypertension.
Dr. Harrington, Dr. Kovacs, Dr. Roth, and Dr. Gurwitz had no relevant disclosures.