Let's talk quickly about fat absorption inhibitors. Orlistat
which is sold as Xenical is sold as an obesity treatment
but it does have reduction in cholesterol too. Now 50% of
patients who take orlistat have a 5% reduction in body mass.
The reduction in diabetes mellitus incidence is also recorded,
probably related to weight loss. There is a modest reduction
in blood pressure and a mild reduction in LDL as well. Now
this reduction in LDL is actually independant of the weight loss.
So, whatever LDL reduction you get from weight loss, there
seems to be a little bit more. In terms of the side effects
of orlistat, the FDA recently released a warning about
hepatotoxicity or possible hepatotoxicity but this flies
in the face of some evidence from the United Kingdom which
used a 94000 patient study to show no causal increase in
hepatic injury with this medication. We are still going to be
very careful in clinical practice, but just to let you know
that there is a bit of a debate on this. There is an increase
in renal failure that's been documented and there is a
theoretical concern about colon carcinoma because we think
that there may be a possible link between the content of
fecal fat and colon cancer although that has'nt been proven
at this point in time. Let's move on to the MTP inhibitors.
This is a new class of drugs. They're fiendishly expensive
but they are now coming on to the market. The prototypical
drug I would say is lomitapide or Juxtapid. It's an oral tablet.
Now it acts on the microsomal triglyceride transfer protein
or MTP, and it is inhibitor of that protein. VLDL and triglyceride
assembly and secretion in the liver is what is being affected here.
It is used for the treatment of familial hypercholesterolemia.
And what it does is it reduces VLDL and all of the non-HDL
fraction of the cholesterol profile. It also will reduce
apolipoprotein B, because remember that apolipoprotein B
are these proteins that are going to be attached to either
VLDL or LDL. It can be used in combination with statins
and some reports indicate up to 60% reduction in LDL cholesterol
with these medications. The adverse events, it may increase
hepatic triglyceride levels and it may cause a transaminitis.
Mipomersen is also an MTP inhibitor and it is a once a week
injection. It targets the messenger RNA for ApoB.
For the treatment of homozygous familial hypercholesterolemia.
We call that HOFH to distinguish it from HEFH which is
heterozygous familial hypercholesterolemia. With this
treatment you get a 25% reduction of LDL. And remember that
these are a group of patients who don't respond well to statins.
So, a 25% reduction in these people is actually pretty good.
It decreases hepatic and plasma ApoB and C-III. It can be used
in combination with statins as well. The adverse events,
once again it may increase hepatic triglyceride
levels, and of course a transaminitis.