Lei Fang and colleagues suggest that clinicians should consider withholding angiotensin converting enzyme inhibitors (ACEIs) or angiotensin receptor blockers (ARBs) because of a potential increased risk of worse clinical outcomes in patients with coronavirus disease 2019 (COVID-19), and they suggest calcium channel blockers as an alternative. The hypothesis behind this suggestion is that the entry point for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the ACE2 receptor and that ACEIs and ARBs have the potential to upregulate ACE2. However, data for this mechanism are largely from animal studies of heart tissue. Human data have not consistently shown increased ACE2 levels.
(A) Mechanism in a healthy individual. (B) Mechanism in an individual with COVID-19. AT1=angiotensin 1. AT2=angiotensin 2. ACE1=angiotensin converting enzyme 1. ACE2=angiotensin converting enzyme 2. AT1R=type 1 angiotensin 2 receptor. AT1-7=heptapeptide angiotensin(1-7). ACEI=angiotensin-converting enzyme inhibitor. ARB=angiotensin receptor blocker. COVID-19=coronavirus disease 2019. SARS-CoV-2=severe acute respiratory syndrome coronavirus 2.
Similar to severe acute respiratory syndrome coronavirus (SARS-CoV), SARS-CoV-2 binds with the ACE2 receptor for intracellular invasion, and the mechanism for acute lung injury during infection has been postulated to be mediated through activation of RAS.
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New England Journal of Medicine – March 30, 2020
Renin–Angiotensin–Aldosterone System Inhibitors in Patients with Covid-19
Uncertain Effects of RAAS Inhibitors on ACE2 in Humans
Key Points Related to the Interplay Between COVID-19 and the Renin-Angiotensin-Aldosterone System
- • ACE2, an enzyme that physiologically counters RAAS activation, is the functional receptor to SARS-CoV-2, the virus responsible for the Covid-19 pandemic
- • Select preclinical studies have suggested that RAAS inhibitors may increase ACE2 expression, raising concerns regarding their safety in patients with Covid-19
- • Insufficient data are available to determine whether these observations readily translate to humans, and no studies have evaluated the effects of RAAS inhibitors in Covid-19
- • Clinical trials are under way to test the safety and efficacy of RAAS modulators, including recombinant human ACE2 and the ARB losartan in Covid-19
- • Abrupt withdrawal of RAAS inhibitors in high-risk patients, including those who have heart failure or have had myocardial infarction, may result in clinical instability and adverse health outcomes
- • Until further data are available, we think that RAAS inhibitors should be continued in patients in otherwise stable condition who are at risk for, being evaluated for, or with Covid-19