There are great research minds working on the Low LDL head scratcher at Resverlogix as we debate.  Bear makes a great point that not all LDL particles are made the same, and how ABET affects each is likely to play a role in this puzzle.  ABET increases HDL, so  what does that do to the various LDL particles  or to rations downstream…. I’m sure I can’t solve it, but it has me pondering….

LDL (bad cholesterol):

Simplistically, we always believe the lower the LDL value the better for cardiac benefit, and the medication we use for LDL lowering is statins:

Patients who started low (well controlled)  and took ABET did better than people who started low and were on placebo (i.e. statin only). Were  the ABET peeps more statin compliant? Is  there is some kind of statin synergy here …  smh.

 Patients starting with a higher LDL didn’t benefit from ABET, but ABET has never been indicated in lowering of the LDLS so again, I go back to ... are they on the wrong statin for their genetics?  What’s up?

And  overall, none of  these participants had a truly bad LDL in my world....so I remain perplexed.

HDL (good cholesterol):

High  HDL  at baseline, no benefit with ABET , but makes  sense; they are not epigenetically broken; healthier, able to exercise, ABET leaves it alone,does no harm.   

Low HDL group at baseline, (Low exercise, dong poorly,epigenetically broken), so ABET fixes that , improves HDL significantly P=0.0001. 

GFR (the higher the better):  This is the interesting one. 

If your eGFR started out below 60, you’re epigenetically broken and you need some readers  and erasers to get to work.  ABET seems to have  done that, with all patients in that arm having less cardiac events when using apabetalone and statin .

If  you’re eGFR was higher, no benefit.  Again, makes  sense, you’re not off kilter yet, so nothing to erase…. But when there is if ABET on board,  theoretically you stay there, that’s good, so yes as someone pointed out… a maintenance situation, put those patients  on ABET if they have Diabetes Mellitus, it’s not causing harm;  will erase as needed.

Summary slide  shows overall reduction in eGFR for all patients on ABET arm  with an  increase in placebo arm AND many of the patients had  had good eGFR to begin with.  So, I imagine ABET does little in the normal  folks, and works phenomenally  to raise those baseline below 60’s up!

So where  is  that GFR data, as has been pointed out ??? I expect it to be stellar if the theory works, so why are they holding that back?  Is  it to go along  with some stellar  CTD data???  Ugh… bring  on the GFR data it’s really important!

Rambling a bit...wine involved... correct me if i missed something.  But mostly, hang in there folks, some interesting stuff is still to come. IMO. DYODD. Hurry up RVX.