ACEi and ARB in COVID-19?
So far from the data coming out of Italy and China, patients with a history of hypertension have worse outcomes when they are diagnosed with COVID-19. (1, 2) Biochemists have discovered that COVID 19 uses angiotensin converting enzyme 2 (ACE2) as an entry point into cells (3, 4). Because of these two findings, some have postulated that medications that interact with the Renin Angiotensin Aldosterone System (RAAS) such as Angiotensin Converting Enzyme Inhibitors (ACEi) or an Angiotensin Receptor Blockers (ARB) may be the culprit for the worse outcomes in patients with hypertension. Here is a very simplified version of part of the RAAS.
When we add an ACEi, it makes sense that the levels of ACE 2 would increase as the levels of Angiotensin II decreased, which is the substrate for ACE 2.
However, an ARB theoretically should increase the levels of ATII therefore decreasing the levels of ACE 2 since it has more substrate to interact.
Some animal models do show an increase in the levels of ACE2 after administration of an ACEi and an ARB (5, 6, 7, 8) while others show no increase (9). In human trials, the effect of ACEi and ARB and ACE 2 is unclear. Some studies show no difference (9, 10). Other studies have shown increases in ACE 2 levels only with some RAAS medications (11, 12). None of these studies looked at patient centered outcomes. They are simply looking at the amount of an enzyme that may or may not predict the severity of the disease course.
Multiple professional organizations such as the American Heart Association and the European Society of Cardiology have made strong recommendations for patients to stay on their antihypertensives at this time based on the benefits we know they convey. There is danger in spreading word to the general public that these medications may worsen COVID-19 infections. We do not want patients to stop their treatment for chronic hypertension. At this time, we should tell our patients to continue taking any ACEi or ARB that has been prescribed to them by their primary care physician.
Zhou F et al. Clinical Course and risk factors for mortality of adult inpatients with COVID-19 in Wuhan, China: A retrospective cohort study. Lancet 2020 Mar 11 pii: S0140-6736(20)30566-3.
Remuzzie A et al. COVID-19 and Italy: what next? Lancet 13 Mar 2020
Zhou P et al
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