Cholesterol, never mind LCAT, try ACAT

Just a quickie. More from the killing fields.

Those poor folks with heterozygous FH are such a playground for cardiologists. My latest accidental find was ACAT inhibition using pactimibe. Medscape describes it this way:

"Pactimibe was in development as an ACAT1 inhibitor, intended to make available more free cholesterol for reverse cholesterol transport, which theoretically could reduce lipid accumulation within atherosclerotic lesions."

Oh, this link works in Safari but not Firefox... Not worth reading, the quote is all you need anyway!

OK, stop foam cell generation and ship out the evil cholesterol (maybe using enhanced LCAT? That'll be next) to HDL for reverse transport. CAPTIVATE-ing idea. I think they were a bit unlucky with this one.

Combined endpoint was deaths, heart attacks and strokes. One out of 438 on placebo, 10 out of 443 on treatment. That's a relative risk of errr, umm... arithmetic fails me.

My biggest worry about drugs being developed based on the lipid hypothesis is that at some time they're going to repeat, again by fluke, the small success of the statins. We'll get a drug which does a little good, a lot of harm and conveniently forget about those who died on pactimibe, torcetrapib or which ever LCAT enhancing drug gets developed. Keeping up the failure rate must be quite difficult, but this continued failure is our best hope for getting some research on heart disease started.

Peter

BTW this drug works really well in genetically hypercholesterolaemic rabbits. No one is suggesting the the WHHL rabbit is a crap model for any sort of arteriosclerosis based on the people injured in this study. OK, I am. It looks like crap model to me.