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washingtonpost.com
Data Support Ultra-Low Cholesterol
By Rob Stein
Washington Post Staff Writer
Wednesday, March 9, 2005; Page A11
A large study has produced the strongest evidence yet that driving cholesterol down to very low levels offers additional protection against heart attacks and strokes, researchers reported yesterday.
The eagerly awaited study involving more than 10,000 at-risk patients showed that using high doses of powerful cholesterol-lowering drugs called statins to slash levels of "bad cholesterol" far below current targets can markedly reduce patients' risks.
The study addresses one of the biggest debates in treating heart disease, the leading cause of death in the United States: How aggressively should doctors and patients use statins to reduce levels of low-density lipoprotein (LDL) cholesterol?
The findings may encourage more doctors to use the drugs to reach ultra-low LDL levels in potentially millions of patients and could lead to new official recommendations if the results of two other studies reach similar conclusions, experts said.
In the new study, researchers gave 10,001 patients whose arteries were already narrowed by heart disease either the standard dose of the statin Lipitor -- 10 milligrams -- or a much higher dose -- 80 milligrams.
After about five years, the cholesterol levels dropped in patients in both groups and their risk for heart attacks and strokes fell. But the LDL levels of those receiving the high dose plummeted the most, hitting an average of about 77 milligrams per deciliter of blood, compared with the standard target of about 100 for the other group. Those who received the high dose also were 22 percent less likely to have a heart attack, stroke or heart failure than those in the standard-dose group.
"We saw a clear benefit," said John. C. LaRosa of the State University of New York Health Science Center at Brooklyn, who led the study. The results, which are being published in the New England Journal of Medicine, were released early yesterday to coincide with a presentation of the data at an American College of Cardiology meeting in Orlando. The study was funded by Pfizer Inc., which makes Lipitor.
A growing body of evidence suggests that driving LDL to very low levels provides significant benefits, and the federal government's National Cholesterol Education Program said in July that those at high risk could consider pushing their levels lower. But the panel stopped short of making an outright recommendation, pending the results of three large studies. The new study is the first of those and the first large one to demonstrate a benefit in heart disease patients who are not experiencing acute problems.
Scott M. Grundy of the University of Texas Southwestern Medical Center at Dallas, who chaired the federal panel, welcomed the findings. But he said the panel probably would wait for the final two studies before issuing new recommendations, particularly because the new study did not show any drop in the death rate. In fact, there was also a small but puzzling increase in the overall number of deaths among those taking the high doses. In addition, the drugs can have side effects, including potentially life-threatening liver problems in a small number of patients.
"Until we get the results of those other two trials and can put it all together, a note of caution is still reasonable," Grundy said.
Other researchers disagreed, saying the evidence is clear enough to change medical practice now.
"There isn't any question left at this point that we should be more aggressive," said Eric J. Topol of the Cleveland Clinic.
Regardless of whether the recommendations are changed now or later, the new findings are likely to encourage more doctors to adopt the approach in the meantime, some experts said.
"This is going to affect millions of people in terms of the practical implications. A lot of primary care physicians are going to look at this result and say, 'Okay, it's time to start doing this,' " said Daniel J. Rader of the University of Pennsylvania.
© 2005 The Washington Post Company

Is anyone else suspicious that they didn't mention the drugs' effects on "good" cholesterol, HDL?

It works!!! ... you are just more likely to die!

http://content.nejm.org/cgi/reprint/NEJMoa050461v1.pdf

This study funded by Pfizer with a whole bunch of ever so independent scientists running it will doubtless be used to trumpet the benefits of Atorvastatin (Lipitor). Strangely the study compared 2 groups - one taking Lipitor ... and the other, taking MORE Lipitor!! There was no control group taking NO Lipitor (because obviously it works, we just want to know how much ... right???)

Anyway, bottom line the group on the high dose died less of CHD ... but more than made up for it with a (slightly) higher death rate from all causes.

Do you think that bit will be widely publicized??

The higher dose being publicized as better in reducing CHD actually caused two more total deaths.

Total deaths due to cardiovascular causes: 126 (80 mg) vs 155 (10 mg)

Total deaths due to other causes: 158 (80 mg) vs 127 (10 mg)

Along with a, not mentioned, 600% increase in liver problems.

The issue is not the level of LDL, but the ratio of LDL to HDL. If you have low HDL, then lowering LDL will improve that ratio. If you have high HDL, your ratio is already good, and there's no need to lower LDL. Nowhere does this study mention any ratios.

To add to Dodger's analysis:


A direct quote from the paper:

"There was no difference between the two treatment groups in overall mortality."

Which sort of deflates that whole argument that "Thousands of lives could be save." Sorry. You won't save a single life.


Another quote:


"A primary event occurred in 434 patients (8.7 percent) receiving 80 mg of atorvastatin, as compared with 548 patients (10.9 percent) receiving 10 mg of atorvastatin, representing an absolute reduction in the rate of major cardiovascular events of 2.2 percent"


Yep, you heard it, a reduction of heart disease by 2.2 percent, by cranking up your Lipitor dose 800%.


Note too, that out of approximately 5,000 patients on the HIGH dose of Lipitor, only 114 patients actually benefitted. (That was the reduction in 'events' on the higher dose. 434 patients still had events, even though their LDL was whacked down to 70.) By my math, that means that ONLY 2% of the people on the high dose of the drug were actually better off. And none lived any longer.

Simple question to ask the MD who wants to put you on the drug. "Will I be one of the 2% who actually benefit?"

That is a suspiciously large increase in death from "other causes." I would not be surprised if those "other causes" were somhow related to taking large amounts of Lipitor.

Thanks A LOT for the link, Malcolm!

What's baffling, is to think of how many doctors will actually read that study, and observe the minuscule (there doesn't seem to be any) benefits to be derived from (As K Walt pointed) increasing by 700% your dose of lipitor.

Most of them will read press releases like the one in the thread starter, and also, of course, the glossy brochures from Pfizer!

As was also pointed out, claiming that this will saves thousands of lives, while the originalo paper clearly shows NO OVERALL MORTALITY BENEFIT, is an outright lie in my opinion.

I'm waiting to see Dr Ravnskov and the Cholesterol Skeptics' rebuttal.

I'm so glad I know this board, to see the other side of the story!

My main though reading was, isn't it about ratio? Why focus on LDL levels.

So, heart desease is defined as blockage and high LDL - an improvement in heart desease would then be noted by lowering LDL, which Liptor does. By definition, since more Liptor lowers LDL more - heart desease is lessened. This studies proved nothing about death from heart desease, only that more Liptor may be bad for you.

Reading this board has certainly taught me to question these sorts of studies.

Gee - and I thought they knew how well statins worked when they first brought them out.

Isn't there still speculation that it is not the statin affect on cholesterol at all that improves cardiac events? In fact, there seems to be a fair amount of evidence that the statins are also anti-inflammatory and that is really how they are helping heart disease. Dr. William Campbell Douglass says he doesn't even check cholesterol levels anymore - opting for inflammation markers like C-Reactive Protein and homocysteine levels. Anti-biotics can be used to cure many cardiac inflammations. Chelation therapy and bromelain supplements can also apparently dissolve plaque. Also there's speculation that it is only oxidized cholesterol that is causing the problem.



Without being a doctor or a medical researcher I'll make a prediction here. The human body is capable of handling low-levels of many toxins - but not high levels. As the dosage of statins increases, so will the death rate.

The oxidized cholesterol idea sounds very likely. The body also needs cholesterol to make hormones etc. Lots of people get depressed when their cholesterol is too low. So I don't think it is the cholesterol that is causing the problem - maybe that it is too changed by heat and that is why it cloggs up our arteries.

Loops