Discover and read the best of Twitter Threads about #sst2

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Here's a question that you might not have considered: how did the dose for #sacubitril/valsartan in #HFrEF get chosen?

Out today is a paper in @JACCJournals led by @RezaMohebiMD that addresses some questions about sac/val dose in HFrEF.

a 🧵…
It's a little known fact that prior to the PH3 PARADIGM trial, a PH2 study in HFrEF was not performed--normally PH2 studies provide target doses for the pivotal outcomes trials.

So how was the dose of sacubitril/valsartan chosen??
The target dose of 97/103 mg twice daily was selected to achieve serum concentrations of valsartan = to those in Val-HeFT and VALIANT while simultaneously achieving 90% neprilysin inhibition in normal individuals.
Read 17 tweets
New in @JACCJournals w @JJheart_doc on intersection of biomarkers & #SGLT2i in #T2D.

Canagliflozin in #CANVAS
⤵️hs-cTnT & sST2 out to 6yrs
⤵️HF & kidney outcomes irrespective of baseline biomarkers
⤵️MACE particularly in those w multiple abnormal markers…
In >3K👥in #CANVAS, canagliflozin (versus PBO) reduced #hscTnT (marker of cardiac injury) & #sST2 (marker of vascular congestion, inflammation & fibrosis) out to 6yrs

Importantly, rather than reducing biomarkers below baseline, #SGLT2i appear to delay longitudinal rise after 1yr
Canagliflozin consistently ↓ a broad set of HF & kidney disease outcomes, irrespective of biomarker profiles.

Interestingly, elevated #hscTnT & #sST2 (& a multi-marker panel) each identified greater *relative* benefits for MACE...including among those without established ASCVD
Read 5 tweets

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