Question I cannot seem to shake...Want to get it out before i forget...but still looking for the info...

Ok, so we know the Crestor (rosuvastatin) group did better than the Lipitor (atorvastatin) group in plaque regression and reverse cholesterol transport.

Regarding the difference between the two for plaque regression, Don said...(in a 2014 transcript that is prob in links library but if not is in my historical posts)...

"...and we do have some very solid theories as to why atorvastatin and rosuvastatin behave different, and it’s a lot to do with the abc-a1 transporter and how each one of those actually affect it."

Back in the day, there was lots of discussion about this abc-a1 transporter difference. 

BUT...were the two groups (Lipitor & Crestor) also significantly different vis a vis inflammation, complement cascades, etc?

The transcripts i was just looking at seem not to specify that...need to find the right sets of slides (with apologies to Bear who no doubt has already pointed to them  - will check)

In another talk, Don gave the relative risk reduction for the combined trials ASSERT, SUSTAIN, and ASSURE (hope i got all those names right), depending on risk factor (low HDL, diabetes, high inflammation...something like that, will find)...ranging from low 40s to high 60s%..

In that talk, which i will tey to find and quote as another reply.. was this RRR limited to rosuvastatin patients.? It is referred to as combined...but maybe that's just combined trials, not combined subgroups.

Either way,  i coud swear i remember some discussion of the possibility that since so many other risk factors were down-regulated, the effect of reverse cholesterol transport may have been less important to the actual RRR goal than to the initial endpoint...thereby making FDA's request for the inclusion of atorvastatin/Lipitor in Phase 3 worthwhile. Meaning...Apabetalone could theoretically still work with Lipitor, though maybe not as strongly as with Crestor, because these other factors are also important in reducing risk.

Is that Just my imagination (once again) running away with me?

My hope is that we saw a strong albeit sadly just shy of statistically significant change in time to FIRST event, preferably for both groups though the Crestor/Rosuvastatin group seems likely to be stronger and more likely to/hopefully rise(s) to statistical significance, PLUS a significant drop in all events (strong RRR) in at least one (preferably more) substantial subgroups, PLUS a statistically significant drop in all-cause mortality. May be a pipe dream, but IF that happened, it might be enough to go straight to approval before another Phase 3.

They only aimed for 30% RRR in the combined group, which the previous three trials exceeded in post-hoc.

I can easily imagine such strong post-hoc numbers in one of the Phase 2 trials being a fluke, but somehow it seems less likely to have been a fluke when all three of them showed such strong results. Don had noted at one point that the BETonMACE trial was only powered at 80% for a 30% RRR...but i think they were expecting that beating 30% would be a non-issue.

Really wondering how we got here, but on the other hand, had the results been as staggeringly good as post-hoc seemed to indicate maybe the trial would have been halted to accelerate approval. Has been known to happen.

Also, still waving the flag for a look at anemia of chronic inflammarion, which affects 16 million people, not as big as cardiovascular or diabetes, but not 100% overlapping and  nothing to sneeze at. Also, the IL-6 hepcidin etc. mechanism is well described and anti-inflammatory compounds are being tested. Seems like a shoe-in.... well maybe.