Doubt Cast on 2 Drugs Used to Lower Cholesterol

[bananas]

http://www.nytimes.com/2008/03/31/business/31drug-web.html?em&ex=1207281600&en=9383ca1e469bba4c&ei=5087%0A

Doubt Cast on 2 Drugs Used to Lower Cholesterol

By ALEX BERENSON
Published: March 31, 2008

CHICAGO — Two widely prescribed cholesterol-lowering drugs, Vytorin and Zetia, may not work and should be used only as a last resort, a panel of four cardiologists told an audience of more than 5,000 people at a major cardiology conference on Sunday.

Instead, physicians and patients should rely more heavily on older cholesterol-lowering drugs called statins, which have proven benefits and can be cheaper, the panel said.

“The strongest recommendation we can make on this panel is to go back to statins,” said Dr. Harlan M. Krumholz, a cardiologist at Yale. “They work.”

Statins include drugs like Lipitor and simvastatin, the generic version of Zocor. But other, lesser-known drugs like niacin should also be tried before Vytorin and Zetia, the panel said.

Vytorin and Zetia are among the top-selling drugs in the world, with combined sales of $5 billion last year. About five million people worldwide, including four million Americans, take the medicines, which have been heavily advertised to consumers in the United States.

The New England Journal of Medicine made a similar recommendation about the drugs in an editorial published on Sunday.

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[fed-up]

1. Cholesterol as a Danger Has Skeptics-NY Times article from Jan 17, 08

why is this buried in the business section??

http://forum.lowcarber.org/showthread.php?t=361367

http://www.nytimes.com/2008/01/17/business/17drug.html

Cholesterol as a Danger Has Skeptics

..
But now some prominent cardiologists say the results of two recent clinical trials have raised serious questions about that theory — and the value of two widely used cholesterol-lowering medicines, Zetia and its sister drug, Vytorin. Other new cholesterol-fighting drugs, including one that Merck hopes to begin selling this year, may also require closer scrutiny, they say.

..
Because the link between excessive LDL cholesterol and cardiovascular disease has been so widely accepted, the Food and Drug Administration generally has not required drug companies to prove that cholesterol medicines actually reduce heart attacks before approval.

They have not had to conduct so-called outcome or events trials beforehand, which are expensive studies that involve thousands of patients and track whether episodes like heart attacks are reduced.

So far, proof that a drug lowers LDL cholesterol has generally been enough to lead to approval. Only then does the drug’s maker begin an events trial. And until the results of that trial are available, a process that can take several years, doctors and patients must accept the medicine’s benefits largely on faith.

..
“LDL lowering, however it occurs, delays development of coronary atherosclerosis and reduces risk for heart attack,” Dr. Grundy said this week. In atherosclerosis, plaque builds up in the arteries, eventually leading to blood clots and other problems that cause heart attacks and strokes.

In the last 13 months, however, the failures of two important clinical trials have thrown that hypothesis into question.

First, Pfizer stopped development of its experimental cholesterol drug torcetrapib in December 2006, when a trial involving 15,000 patients showed that the medicine caused heart attacks and strokes. That trial — somewhat unusual in that it was conducted before Pfizer sought F.D.A. approval — also showed that torcetrapib lowered LDL cholesterol while raising HDL, or good cholesterol.

..
Then, on Monday, Merck and Schering-Plough announced that Vytorin, which combines Zetia with Zocor, had failed to reduce the growth of fatty arterial plaque in a trial of 720 patients. In fact, patients taking Vytorin actually had more plaque growth than those who took Zocor alone.

..

Without data from events trials for Zetia and Vytorin, no one can be certain if the drugs help or hurt patients. But Merck and Schering did not begin an events trial for the drugs until 2006, nearly four years after the F.D.A. approved Zetia. That trial will not be completed until 2011.

Dr. Robert M. Califf, the vice chancellor for clinical research at Duke University, and a co-lead investigator on the Zetia trial still under way, said companies should have started the trials more quickly. “Outcome trials ought to start when you know you’re going to get on the market,” he said.

[TZ]

2. Its not so much doubt as cholesterol being an issue

But the effectiveness of the two drugs vytorin and zetia. Some of these statins have MORE than proved their worth. For instance I take Crestor, and it has been shown SO effective in preventing heart attacks and other cardiovascular events that they actually stopped the clincial trials EARLY because they have such good data.
Thats why this is in the business section. You aren't going to find ANY MD who doesn't think that Cholesterol, triglycerides and other factors aren't huge risks for heart attacks

[bananas]

3. Thanks for that forum link, one of the posts linked to this Business Week article

(They posted a different snippet from the Business Week article)

http://www.businessweek.com/magazine/content/08_04/b4068052092994.htm?campaign_id=rss_daily

Cover Story January 17, 2008, 10:00AM EST
Do Cholesterol Drugs Do Any Good?
Research suggests that, except among high-risk heart patients, the benefits of statins such as Lipitor are overstated

by John Carey

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IRRELEVANT LDL?

If cholesterol lowering itself isn't a panacea, why is it that statins do work for people with existing heart disease? In his laboratory at the Vascular Medicine unit of Brigham & Women's Hospital in Cambridge, Mass., Dr. James K. Liao began pondering this question more than a decade ago. The answer, he suspected, was that statins have other biological effects.

Since then, Liao and his team have proved this theory. First, a bit of biochemistry. Statin drugs work by bollixing up the production of a substance that gets turned into cholesterol in the liver, thus reducing levels in the blood. But the same substance turns out to be a building block for other key chemicals as well. Think of a toy factory in which the same plastic is fashioned into toy cars, trucks, and trains. Reducing production of the plastic cuts not only the output of toy cars (cholesterol) but also trucks and trains. In the body, these additional products are signaling molecules that tell genes to turn on or off, causing both side effects and benefits.

Liao has charted some of these biochemical pathways. His recent work shows that one of the trucks, as it were—a molecule called Rho-kinase—is key. By reducing the amount of this enzyme, statins dial back damaging inflammation in arteries. When Liao knocks down the level of Rho-kinase in rats, they don't get heart disease. "Cholesterol lowering is not the reason for the benefit of statins," he concludes.

The work also offers a possible explanation of why that benefit is mainly seen in people with existing heart disease and not in those who only have elevated cholesterol. Being relatively healthy, their Rho-kinase levels are normal, so there is little inflammation. But when people smoke or get high blood pressure, their Rho-kinase levels rise. Statins would return those levels closer to normal, counteracting the bad stuff.

Add it all together, and "current evidence supports ignoring LDL cholesterol altogether," says the University of Michigan's Hayward.

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