PRESENTED BY
PATRICK MARK

Presentation Summary

Written by Jasna Trbojevic-Stankovic
Reviewed by Patrick Mark

Angiotensin-converting enzyme (ACE) inhibitors and angiotensin receptor blockers (ARBs) are used by 6.6 million people worldwide for the treatment of high blood pressure and diabetic kidney disease. Recently, it has been hypothesized that these widely prescribed medications could increase the risk of severe viral pneumonia with respiratory failure and even death in patients with new coronavirus disease (COVID-19). A recently published retrospective, multicentre cohort study, in 191 adult patients with COVID-19 identified hypertension, diabetes and coronary heart disease as the most prevalent comorbidities (1). Their presence in this patient cohort was associated with worse outcome, bringing up the question whether it was the diseases themselves, or the concomitant therapeutic agents these patients have been using that predisposed them to a worse outcome (2).

Fifteen years ago, during the outbreak of the severe acute respiratory syndrome (SARS), which was also caused by coronavirus (CoV), the ACE2 has been identified as a crucial SARS-CoV receptor (3). The spike protein of SARS-CoV-2 binds to ACE2 to enter target cells – the epithelial cells of the lung, kidneys, blood vessels and intestine (2; Figure 1).

Figure 1. The role of ACE2 in SARS CoV-induced lung injury (3)

The expression of ACE 2 is substantially increased in patients with hypertension and/or diabetes treated with ACE inhibitors or ARBs. Both ACE inhibitors and ARBs are cornerstone therapeutics for hypertension, chronic kidney disease, diabetic kidney disease and heart failure. At the start of the COVID-19 epidemic it was speculated that these drugs might facilitate viral entry to the lung, although there were no clinical data to support this interesting hypothesis and it was equally plausible that ARBs in particular may convey some protection from COVID-19 infection. In the absence of data, there was a call for calm reflection on how basic science may inform clinical practice in the face of a global pandemic (4).

Early on in the pandemic, most professional societies (e.g. European Society of Cardiology, UK Renal Association advised against stopping the ACE inhibitors or ARBs in patients without symptoms of COVID-19. Observational data now support that there is no evidence that these drugs increase risk of COVID-19 infection (5).

Recommendations were less clear for patients with proven COVID-19 but recent reports suggest that these drugs are not associated with worse outcomes in COVID-19 (6).

Therefore, unless there is a clear reason to discontinue these ACE inhibitors or ARBs in patients with COVID-19 (hypotension, severe acute kidney injury) it appears reasonable to continue them. In patients who do discontinue these drugs in the setting of severe acute illness it is important to plan when to recommence therapy when there a strong evidence-based indication for their use.

References

1. Zhou F, Yu R, Fan G. et al. Clinical course and risk factors for mortality of adult inpatients with COVID-19 in Wuhan, China: a retrospective cohort study. Lancet 2020;395:1054-1062

2. Fang L, Karakiulakis G, Roth M. Are patients with hypertension and diabetes mellitus at increased risk for COVID-19 infection? 2020;8(4):E21.

3. Kuba K, Imai Y, Rao S. Et al. A crucial role of angiotensin converting enzyme 2 (ACE 2) in SARS coronavirus-induced lung injury. Nature Medicine 2005;11(8):875-879.

4. Sparks M.A, South A, Welling P. et al. Sound science before quick judgement regarding RAS blockade in COVID-19. CJASN 2020. Available at: https://cjasn.asnjournals.org/content/clinjasn/early/2020/03/30/CJN.03530320.full.pdf

5. Mancia G., Rea F., Ludergnani M., Apolone G., and Corrao G. Renin–Angiotensin–Aldosterone System Blockers and the Risk of Covid-19. NEJM DOI: 10.1056/NEJMoa2006923

6. Mehra M.R, Desai S.S., Kuy S., Henry T.D., Patel A.N. Cardiovascular Disease, Drug Therapy, and Mortality in Covid-19. New England Journal of Medicine 0.1056/NEJMoa2007621

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