I think the 0.6% plaque reduction goal in the ASSURE trial was simply based upon plaque regression observed in other past IVUS trials and was simply used for trial design and trial statistical powering purposes. Similar to how BETonMACE trial design and statistical powering was done assuming a 30% relative risk reduction. The actual % change in plaque or %RRR in MACE isn't as important as the statistics. If the change is not statistically significant, it doesn't count. Sad but true. 

 

Even if the stats supported apabetalone mediating a statistically significant reduction in plaque vs. the baseline plaque value in the apabetalone group, the fact that the placebo group experienced such a surprising plaque reduction benefit as well is the big elephant in the room. Would you really call ASSURE a trial success if the amount of plaque reduction in the apabetalone group was not significantly different than that observed in the placebo group?

 

On a side note, I suggest folks look at pages 1-11 of the ASSURE study document (see this document) I reference in an earlier post. First off, you can see that a 0.6% change was never mentioned as a goal. Like I indicated above, it's the stats not the absolute change that are most important. Second, it appears that there were several pre-specified sub-group analyses for the plaque reduction. From page 8:

 

"The primary endpoint, change in PAV within the active RVX000222 treatment group, was analyzed for the following

subgroups for the FAS and PP Population:

• Baseline PAV (at or above or below the overall median)

• Baseline HDL-C (at or above or below the overall median)

• History of diabetes mellitus (yes or no)

• Gender (male or female)

• Age (≥65 or <65)

• Statin Use (atorvastatin or rosuvastatin)

• Baseline Apo-A1 (at or above or below the overall median)

• Baseline large HDL (nuclear magnetic resonance) (at or above or below the overall median)

• Baseline hs-CRP (at or above or below the overall median)"

 

Then on page 10, it states:

 

"Subgroup analyses of the primary endpoint demonstrated significant reductions in PAV at Week 26 in

mellitus, and in patients with large HDL and HDL-C that were below the baseline median."

 

That's really interesting. So even though several of the sub-group analyses (pre-specified I think) showed positive results in plaque reduction, the ASSURE trial was still deemed a failure. This makes me wonder how the BETonMACE sub-group analyses of primary outcome will be viewed if the analysis on the total population fails to meet statistical significance, as we had discussed in this thread yesterday. It's still not clear to me if the rosuvastatin sub-group analysis (rosuvastatin vs. rosuvastatin/apabetalone) would be considered a success with statistcal significant %RRR if the combined statin arm fails to achieve statistical signifigance. If pre-specified primary outcome analyses of ASSURE held no weight, should we expect any different in BETonMACE. I'm still confused on this.

 

BearDownAZ