Jonzobot wrote "I think it's a great hypothesis to confirm. BUT the numbers are low. 4 vs 12 events (treated vs placebo) for narrow MACE; 6 vs 15 for broad MACE. It's obviously promising but I supect it requires confirmation, IMO"

Great observation. A 3-point MACE occurred in 4 of 142 apbetalone patients taking an SGLT2i and in 12 of 145 placebo patients taking an SGLT2i. A 5-point broad MACE occurred in 6 of 142 apbetalone patients taking an SGLT2i and 15 of 145 placebo patients taking an SGLT2. Importantly, patients only needed to be taking SGLT2i for at least 30 days during trial and prior to MACE to qualify for this analysis. This is very different than the assumption that these patients were all on SGLT2i for the entire trial duration. More on this below.

Growacet wrote "The problem is that the trial started in 2015....when sgl2s weren't around, some patients were put on them while BETonMACE was running and if I understand correctly they're inclusion as SOC for some patients had a significant impact on the event rate in the placebo arm."

Correct. Some patients started on the SGLT2i during some point in the trial and were not taking SGLTi at beginning on the trial. The "baseline" patient data shared yesterday shows that 150 of 1212 (12.4%) apabetalone patients and 148 of 1206 (12.3%) placebo patients were on SGLT2i. However, a footnote indicates that these 298 patients were categorized as receiving any SGLT2i drug during study. From above, we see that 287 of these 298 received SGLT2i for at least 30 days and prior to MACE. But how long were these 287 actually on SGLT2i? How many were on it at true baseline?

In the BETonMACE design and rational paper, the baseline table lists 122 of the 2425 patients on SGLT2i. Interestingly, 115 of these were non-CKD and only 7 were CKD. Although this paper was only published recently, I hypothesize that these patients were indeed the ones on SGLT2i at true baseline. These are the same numbers listed in the late August/early Sept 2019 ESC poster and the early November ASN poster.

However, in the March 2019 ACC poster, it indicates that 266 of the 2425 patients were on SGLT2i. 24 of these 266 were in the cognition subgroup (467 patients age 70 or older); 13 of those 24 had baseline MoCA score <25.

And in the July 2019 AAIC poster, it indicates that 290 of the 2524 patients were on SGLT2i. 28 of the 290 were in the cognition subgroup; 14 had baseline MoCA>25 and 14 had baseline MoCA<25.

Although the SGLT2i syndergy is VERY exciting, some caution is warranted due to the low number of observed MACE events as well as the uncertaintly as to how long the patients were on SGLT2i.

BDAZ