Angiotensin-converting enzyme inhibitors and angiotensin-receptor blockers benefits outweigh the risks in COVID-19 hypertensive patients.

To the Editor,

We read with interest the article published by Wang et al. in Medical Virology journal. The meta‐analysis of 26 studies revealed that treatment with angiotensin‐converting enzyme inhibitors (ACEIs) and angiotensin‐receptor blockers (ARBs) is significantly associated with lower risk of mortality in coronavirus disease 2019 (COVID‐19) infected hypertensive patients. We are in total agreement with these findings and we want to represent the mechanisms that can support these results.

ACE2 receptor is the key mediator for viral entry into the human cells. Meanwhile, it is an important regulator of the renin‐angiotensin‐aldosterone system, that acts by hydrolyzing angiotensin I to angiotensin (1‐9) and angiotensin II to angiotensin (1–7). The dual roles played by ACE2 as the receptor for severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) and as a protector against the harmful effects of angiotensin II, has caused controversy regarding the continued use of ACEIs and ARBs during the outbreak as they result in ACE2 receptor upregulation. Recently, recommendations have been released supporting the continued use of these potential antihypertensive agents throughout the pandemic due to insufficient evidence of their harmful effects. ,

We hypothesize that ACEIs and ARBs use for COVID‐19 hypertensive patients provide more benefits than harms and might be the drug of choice for both blood pressure control and viral treatment.

First, cytokine storm syndrome, characterized by increased inflammatory mediators is considered one of the main causes of increased mortality associating COVID‐19. The anti‐inflammatory and pleiotropic effects of ACEIs and ARBs have been proven in patients with hypertension and coronary heart disease. This supports the beneficial impact of ACEs and ARBs on the novel virus rather than harm.

Second, COVID‐19 infection is associated with cardiovascular complications in many patients which are more common among hypertensive patients. Although, the underlying mechanism remains incompletely understood, endothelial dysfunction seems to represent the primary step in COVID‐19 associated cardiovascular risk due to ACE2 expression on endothelial cells. Studies in patients with cardiovascular diseases have demonstrated improved flow‐mediated dilatation, a marker of endothelial function with ACEIs and ARBs use, providing convincing evidence of their potential benefits on endothelial dysfunction. ,

Third, coagulopathy has been manifested in up to 50% of COVID‐19 severe cases especially the hypertensive patients. By downregulating the ACE2, SARS‐COV‐2 increases angiotensin II, that in turn, increases thrombin formation and impairs fibrinolysis. Recent in vitro and in vivo studies support the anti‐thrombotic and fibrinolytic characteristics of ACEIs and ARBs. ,

In conclusion, the benefits of ACEIs and ARBs use during COVID‐19 can greatly outweigh the risks, which supports Wang et al. findings. In the absence of a suitable vaccine and while facing a viral second wave, some clinical trials are underway to evaluate the possibility of using these already FDA approved medications for treatment of the novel virus, especially in hypertensive patients that represent a well‐established risk category for the infection.

CONFLICT OF INTERESTS

The authors declare that there are no conflict of interests.