Zetia, are things getting better?

I like zetia.

It had a lot going for it. No bungling in the advertising department this time. They must have learned their lesson from the crash and burn of torcetrapib, the standard fate of drugs without an X, Y or Z in their name. So it was the big Z for Zetia. Even the drug name, ezetimbe, has that cool z... It has overtones of relaxing, good times, not in the least difficult, eze in fact.

And it's turned to be one of the best cholesterol lowering drugs ever. I don't have the full study (does anyone?) I'm just looking at the press reports and Dr Nissen's squirming featured on Dr Eades' blog. But the best thing is:

I don't think they killed anyone with Zetia.

This is a big improvement on both torcetrapib and clofibrate. I've no idea about the actual fatalities, and I doubt the Zetia study was powered to detect changes in overall death rate anyway. Total mortality always seems something of a gamble in cholesterol lowering trials. Mind you, just thinking aloud, there seems to be no talk of "a trend towards improved survival", so perhaps there was an non significant increase in fatalities, I hope not. As I say, I don't have the numbers. But it seems impossible to spin this study to be pro Zetia. Tragic.


Apart from the bankruptcy of the lipid hypothesis, why did Zetia fail?

That's pretty obvious. Have a look at this paper. Those poor hyper responders to dietary cholesterol were fed eggs. Their cholesterol went up. Oh no. Except it was the "good" lipoproteins which increased.

"These findings suggest that the increases in LDL-C and HDL-C due to increased egg consumption in hyper-responders are not related to an increased number of LDL or HDL particles but, to an increase in the less atherogenic lipoprotein subfractions."

Similarly in this study they found

" the LDL peak diameter was increased during the EGG period for all subjects."

I believe increased LDL particle diameter is considered to be a Good Thing.

Now if Zetia stops you absorbing your breakfast eggs, you don't have to be a genius to predict what it will to the "atherogenicity" of your lipids.... Oh, but your calculated LDL goes down with Zetia. Yawn again.

Anyway, Zetia is less frankly toxic than some the previous non statin cholesterol lowering agents, for what that's worth.

Still useless. How did a drug with such a cool name fail?

Peter