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BMJ 2020; 368 doi: https://doi.org/10.1136/bmj.m406 (Published 31 January 2020) Cite this as: BMJ 2020;368:m406

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Switching from ACE inhibitors to ARB in preventing severe course of COVID-19

Dear Editor,

Angiotensin II receptor blockers (ARB) are currently debated as an option for treatment of coronavirus disease 2019 (COVID-19).

Angiotensin I is converted to Angiotensin II by angiotensin converting enzyme (ACE). Angiotensin II is responsible for vasoconstriction and proinflammatory effects mediated by angiotensin receptor type I (AT1). Angiotensin converting enzyme 2 (ACE2) converts Angiotensin II to Angiotensin 1-7 which on the contrary exhibits vasodilatory and antiinflammatory effects and outweights the effect of angiotensin II mediated by AT1. Patients on chronic treatment with ACE inhibitors upregulate both AT1 receptors and ACE2 that are affected by diminished amount of Angiotensin II produced by alternative enzymatic pathways (e.g. by chymases), nevertheless still in a balanced manner. It has been demonstrated that ACE2 serves as a binding site for SARS-CoV-2 enabling viral entry. Continuous elimination of ACE 2 from the cell surface decreases residual ACE2 activity shifting the balance towards AT1 activation causing pulmonary vasoconstriction, excessive inflammation and finally acute lung injury. At the same time unoppossed effect of angiotensin II leads to mycardial injury and elevation of blood pressure which are observed in the most severe cases.

Therefore switching from ACE inhibitors to ARB might be beneficial in patients at risk or with COVID-19 in prevention of such sequelae when they are already on therapy affecting the Renin-Angiotensin System. Both ACE inhibitor and ARB have shown comparable long-term benefit in prevention of adverse cardiovascular events which makes the switch justifiable, moreover with reduction of cough which can be misinterpreted as one of COVID-19 signs.

On the contrary switching to other antihypertensive drugs at the moment of upregulation of AT1 receptors and ACE2 or even starting the treatment with ARB in ARB-naïve patients is controversial.

References:
1, https://www.bmj.com/content/368/bmj.m406/rr-19
2, Kuba, Keiji et al. Lessons from SARS: control of acute lung failure by the SARS receptor ACE2. Journal of Molecular Medicine 84 (2006): 814-820.
3, Zheng, Y., Ma, Y., Zhang, J. et al. COVID-19 and the cardiovascular system. Nat Rev Cardiol (2020). https://doi.org/10.1038/s41569-020-0360-5

Competing interests: No competing interests

13 March 2020
Sikora Jiri
Cardiologist
Cardiovascular and Transplant Surgery Centre
Pekarska 53, 656 91 Brno, Czech Republic