Potential role of Sacubitril/valsartan
Sacubitril/valsartan is the first of a new class of drugs with a
therapeutic indication for the treatment of chronic symptomatic heart
failure with reduced ejection fraction. Sacubitril is a neprilisin
inhibitor (NEPi), valsartan an angiotensin II receptor antagonist (ARBs)
(64). Based on the considerations described above, the association
sacubitril/valsartan could be an important therapeutic solution to
combat COVID-19 infection. The use of the sacubitril/valsartan
association could be of clinical benefit for several reasons, in
particular the antagonism on the AT-1 receptor mediated by valsartan
would lead to increased receptor occupation by the Ang II of the AT-2
receptor with antifibrotic, antiflammatory, antihyperproliferative and
vasodilating effects with potential benefits on both pulmonary lesions
caused by fibrotic tissue and cardiac damage caused by COVID-19. In
addition, the actions of Ang-II on the AT-1 receptor, which mediates
vasoconstriction, profibrotic and hyperproliferative effects, are
blocked. Finally
Angiotensin II can cause increased inflammation through production of
IL-6, TNF-α and other inflammatory cytokines mediated by AT-1.
(65)(66)(67) It is known that in the more severe stages of COVID-19
infection there is a decrease in ACE-2 which plays a protective role. In
fact, ACE-2 synthesizes Ang 1-7 and Ang 1-9 with known
anti-inflammatory, vasodilating, antifibrotic and antihyperproliferative
effects. (68)(69) The antagonism on AT-1 receptors leads to a
compensatory increase of ACE-2. (70) Finally, after ARBs administration
the response to hypertrophic growth induced by TNF-a is significantly
attenuated (71) (Figure 1 ).