Hi @LeftYahoo, Great points. As you mentioned, FDA approval of...

Hi @LeftYahoo,

Great points. As you mentioned, FDA approval of Astra Zeneca's dapagliflozin (Farxiga) was in 2020 i.e. for risk reduction of CV death/ hospitalisation in class II-IV adults with HFrEF. The FDA approval of the label extension of empagliflozin (Jardiance) to the HFrEF indication in CHF was in August, 2021.

On your question: " For example, it would be interesting to know how many patients had to be enrolled in ph3 SGLT2i trials to get the label extension?", the Farxiga extension (to the HFrEF population in CHF) was based on the DAPA-HF trial. It looks like the trial covered 4,744 adult patients with CHF with HFrEF (at least 40% reduction over a run-in period). And the primary endpoint was a composite i.e. CV death or hospitalisation for HF or an urgent HF visit. But it's difficult to find detail on the breakdown of the hospitalizations that focusses solely on the MACE hospitalizations - there's a great deal of effect in the impact on outpatient worsening of HF (e.g. as treated in SOC with intensifying oral loop or, more importantly, intravenous diuretics).

See, for example: https://pmc.ncbi.nlm.nih.gov/articles/PMC7580857/

The Jardiance extension was based on results from the EMPEROR-Reduced Ph III i.e. intent to treat population was 3,730 adults (with and without type 2 diabetes) who had HF (class II, III or IV) and a left ventricular EF of 40% or less. For this one, Boehringer Ingelheim and Lilly claimed a relative risk reduction of the primary endpoint (time to cardiovascular death or hospitalization for heart failure) by 25% (i.e. a 5.3% absolute risk reduction, 0.75 HR, 0.65-0.86 95% CI) versus placebo, & regardless of background HF SOC. Again, this one was a composite primary too. Again, reduction in risk of outpatient worsening HF events was a significant factor i.e. it showed a decrease in the need for intravenous diuretic intensification in the outpatient setting and a corresponding lower risk of worsening heart failure events.

So re " They have both a mortality and a hospitalization benefit in HFrEF patients though the literature suggests benefits become more nuanced and side-effects of more concern in class IV patients.", there's some wiggle room I feel on the extent to which the total hospitalization benefit in the SGLT2 inhibitor trials was masking the real impact on MACE events. I think this is also where the Revascor LVAD patient i.e. end-stage patient trial becomes particularly important in the current Type 2 discussions with the FDA.

I guess we'll see how important shortly.

Cheers,
GLTALTH