Figure
1 : Sacubitril/Valsartan mechanism of action and biological
effects
The beneficial
effects of NEPi are attributable to decreased degradation of natriuretic
peptides. Natriuretic peptides cause vasodilation by stimulating the
guanylate cyclase receptor to produce cGMP. In addition, sacubitril
administration is known to decrease NT-proBNP, which in severe cases
COVID-19 is increased. In patients with COVID-19, with and without
symptoms attributable to pneumonia, there is evidence of a significant
increase in NT-proBNP, regardless of left ventricular dysfunction.
Indeed, studies show that NT-proBNP levels are also the results of acute
renal lesions and pro-inflammatory molecules such as interleukin-1 and
C-reactive protein,(72) In addition, natriuretic peptides act to
suppress the renin-angiotensin and sympathetic systems and decrease
endothelin secretion. In addition, as mentioned above, natriuretic
peptides also exert anti-inflammatory, antifibrotic and antihypertrophic
effects. In particular, some evidence shows direct mediated
anti-inflammatory effects. In particular, some studies associate the BNP
peptide with an important inhibitory effect on the activation of
inflammatory NALP3, which is related to the reduction of BNP-induced
NF-kB and ERK1/2 activation. In addition, for this class of drugs acting
on RAS, there is potential indirect protection against SARS-CoV-2. In
fact, patients with cardiovascular disease are at high risk of
pneumonia, studies show that the use of drugs that block RAS decreases
this risk. (73)(74) On the basis of the evidence described and in
relation to the hypotheses suggested by us, the use of the
sacubityl/valsartan association in patients with COVID-19, especially in
severe cases, could be of therapeutic benefit, with cardioprotective,
anti-inflammatory and antifibrotic effects capable of fighting lung
damage, through an increase in the natriuretic peptide system and a
decrease in the effects of AT-1 receptor-mediated Ang-II.
Well-structured clinical studies are required to confirm these
hypotheses.