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What happens to BNP when a person is started on #sacubitrilvalsartan?

#BNP should go up, right?

Thanks to work by @pmyhre in our group, we have some new and interesting data.

A ๐Ÿงต, read on! ๐Ÿ‘‡
When the #PARADIGM-HF study was published, one of the things immediately noticed was the increase in BNP that occurred after being started on sacubitril/valsartan.

This is because through effect of sacubitril, neprilysin is inhibited. Why might this lead to an increase in BNP?
#Neprilysin is a ubiquitous metalloproteinase that assaults BNP (among other targets including ANP and CNP) and cleaves it in numerous places as shown.

Note that in BNP, there are cleavage sites that involve numerous places where immunoassays for measurement of BNP may bind.
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