Cholesterol Levels

[quote]Res Judicata wrote:
And don’t give me one-off anecdotal evidence. That means jack shit. Show me a clinical trial. [/quote]

I’m not interested into getting into the whole internet argument thing here but there’s a considerable number of doctors now stating that there’s never been a clinical trial that’s shown a link between fat and cholesterol and there’s never been a clinical trial that’s shown a link between cholesterol and heart disease.

OP: Try having a look at http://www.fathead-movie.com/ and the doctors he links to; I’ve got the movie “Fat Head” and it’s very interesting, funny and educational; it’s more of a diet thing but it goes into statins and the whole lipid hypothesis.

Also see http://www.proteinpower.com/drmike/statins/anatomy-of-a-statin-ad/ for the scope of the whole statin business, how it’s pushed and what they can insinuate but can’t legally claim.

I’m a lawyer who previously trained as a scientist. I don’t actually give advice on FDA matters, but I’ve taken seminars on these issues and had an opportunity to read the advice given by lawyers who specialize in this area. I’ve also read nearly all of the statin trial primary papers up to a couple of years ago.

I know what drug companies are allowed to say and what they’re not allowed to say. If left to their own devices they’d say a lot of stuff. But they really, really don’t want FDA on their case. It’s expensive, bad PR and all-around sucks. Ironically, the rules work both ways-- they can’t say things clearly supported by the evidence if its not on the label, for example.

The lipid hypothesis is about a well established as gravity. There are some questions around the edges – the role of the inflammatory process is really only now being understood. A recent Crestor trial showed that even people with “normal” LDL-C but who have an elevated marker for inflammation (HsCRP) can benefit from statins.

There are two major bases for the relationship between LDL-C and heart attack risk: longitudinal studies like the Framingham heart study and interventional studies from as early as the 80s. Framingham basically took a large patient population and followed them for years as they lived their lives. It was non-interventional, side from their regular medical care. Through statistical analysis it estblished baseline risk for various things, like heart attack, and what factors correlated with those risks. High cholesterol turned out to be a HUGE risk factor, and its where we get the risk categories. It’s why we now the OP is at high risk unless something changes.

We also know that people with genetic cholesterol disorders have a very high risk of stroke and heart attack. And they have lots of atherosclerosis.

The interventional studies – double blind, placebo or comparator-controlled – established early on that lowering cholesterol or LDL-C (depending on the era and the tests available) reduced these risk. And I’m talking before statins – niacin, bile-acid resin etc. Then lovastastin came out, and it worked better than anything else with a better side-effect profile. (The older drugs had some NASTY side effects and tolerability issues).

Interestingly, it’s not clear from the interventional studies whether raising HDL-C has much of an effect on anything. But the jury’s still out on that one.

[quote]Res Judicata wrote:
The lipid hypothesis is about a well established as gravity. There are some questions around the edges – the role of the inflammatory process is really only now being understood. A recent Crestor trial showed that even people with “normal” LDL-C but who have an elevated marker for inflammation (HsCRP) can benefit from statins. [/quote]
Possibly because statins have mild anti-inflammatory effects.

At one time not very long ago it was about as well established as gravity that stomach ulcers were a result of over active acid production. We now know that this was entirely WRONG! Stomach ulcers are caused by h. pylori overgrowth and are best treated with antibiotics.

You should go back and read your own point. High cholesterol may be CORRELATED with atherosclerosis, but there is no evidence it is CAUSATIVE.

it reduced the risk, but by how much? It turns out the reduction in risk is measurable BUT NOT SIGNIFICANT. For example, if your risk of a disease is 1 in 5000, and your risk drops to 1 in 5500, did your risk change enough for the treatment to be considered useful? I think you’ll find that for the prevention of heart attack with statins the number is ridiculously low. It’s measurable, but low.

Anybody who thinks they need to go on statins needs to do all the research and choose the best option for them, remembering that the people who sell drugs are not going to say anything that reduces their profits.

Had to chime in here guys since no one has made the recommendation to check oxidized LDL and other (more predictive) markers of cardiovascular risk. A simple lipid panel is too simplistic to properly ascertain risk.

http://www.bhlinc.com/clin_test.php

TZ

[quote]Res Judicata wrote:
I’m a lawyer who previously trained as a scientist. I don’t actually give advice on FDA matters, but I’ve taken seminars on these issues and had an opportunity to read the advice given by lawyers who specialize in this area. I’ve also read nearly all of the statin trial primary papers up to a couple of years ago.
[/quote]

Have you seen the data on Baycol? How do you explain that?

[quote]Res Judicata wrote:
And don’t give me one-off anecdotal evidence. That means jack shit. Show me a clinical trial. [/quote]

Baycol went through Phase III Clinical Trials and was released with full FDA approval.

Baycol (cerivastatin) is one of the reasons we have post marketing surveillance. There are some small risks that you can’t really see until you give it to a large enough population. The studies are designed to give you a good view of the risks, but you can only make them so large.

That drug was enormously potent and effective, but has a crappy safety profile. All statins have a small risk of rhabdomyalysis that does not seem to be dose-dependent. It turned out the Baycol had multiple times the risk of other statins for that side-effect. It was still a pretty small risk, but more (several times)the others. It took post marketing surveillance to pick that up and that’s why Baycol was removed from the market.

It’s not the first and it’s not the last drug that will happen with.