From FoodNavigator.com  

A combination of fish oils, red yeast rice and other lifestyle changes reduced cholesterol levels by the same amount as a daily statin pill, according to new research.

From  NaturalNews.com

Patients who take the cholesterol drug torcetrapid, intended to increase levels of HDL (”good”) cholesterol and lower LDL (”bad”) cholesterol levels, have a 58 percent higher risk of death than similar patients who do not take the drug, according to a study led by researchers at the Heart Research Institute in Sydney and published in the New England Journal of Medicine.

Researchers studied 15,067 participants, all considered to be at high risk of cardiovascular disease. All the patients were treated with the cholesterol-lowering drug atorvastatin, while half were also treated with torcetrapid.

Torcetrapid is marketed by Pfizer, as is atorvastatin (under the brand name Lipitor).

Patients receiving both drugs had a 58 percent higher chance of dying and a 25 percent higher chance of experiencing cardiovascular events such as heart attacks than those who were treated only with atorvastatin.

Torcetrapid is one of a new class of drugs called cholesteryl ester transfer protein (CETP) inhibitors. Unlike older cholesterol drugs, which only lower LDL levels, CETP inhibitors are intended to raise HDL levels at the same time. The drugs function by blocking the action of a protein that transfers cholesterol from HDL to LDL, thus forcing the cholesterol to remain in HDL form.

In the recent study, torcetrapid was found to raise HDL levels by an average of 72.1 percent, and lower LDL levels by an average of 24.9 percent.

Scientists are still unclear why torcetrapid appears to increase patient death rates and heart attack risk. While the drug is known to raise blood pressure, many of the patients who died in the recent study actually had blood pressure levels below normal.

Researchers have hypothesized that the drug may increase the levels of a hormone involved in regulating blood pressure, and that this may lead to stress on the cardiovascular system.

Merck and Roche Holding have placed the development of their own CETP inhibitors on hold, pending the results of further trials on torcetrapid.

From New York Times

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.

Both the panel and the editorial were timed to coincide with the release of full results from a two-year clinical trial that showed that the drugs failed to slow, and might have even sped up, the growth of fatty plaques in the arteries. Growth of those plaques is closely correlated with heart attacks and strokes.

Merck and Schering-Plough, the companies that make Vytorin and Zetia, said on Sunday that they disagreed with the recommendations. Vytorin and Zetia have been proved to lower cholesterol and are valuable treatments for patients, said Dr. Rick Veltri, vice president of the Schering-Plough research institute.

We feel that nothings changed, Dr. Veltri said.

On Monday, shares of Merck fell $6.77 to $37.74 while Schering fell $5.07 to $14.40 at mid-day.

The stakes of the debate are high both medically and financially. The drugs produce about 70 percent of Schering-Ploughs profit, according to analysts.

Prescriptions for the medicines have already dipped by about 15 percent since January, when preliminary results were disclosed from the trial discussed in detail on Sunday. Still, the drugs are very widely used, with about three million prescriptions written each month in the United States alone.

Unlike statins, which block the liver from making cholesterol, Zetia works by blocking the intestine from absorbing cholesterol in food. Vytorin is a single pill that combines Zetia with simvastatin, or Zocor.

LDL cholesterol, the harmful kind, is known as a risk factor for heart disease, and so doctors have generally assumed that lowering LDL cholesterol would reduce the risk of heart attacks and strokes.

But proving that a drug actually cuts those risks requires an expensive, multiyear clinical trial involving 10,000 or more patients. Those studies, called outcomes trials, have been conducted for statins, and they have proved that patients taking those drugs do have a reduced risk of heart disease. No such outcomes trials exist for Vytorin and Zetia.

The Food and Drug Administration initially approved Zetia in 2002 on the basis of trials that lasted no more than 12 weeks and covered only 3,900 patients.

In 2006, four years after Zetia reached the market, Merck and Schering began enrolling patients in their own outcomes study, which compares people taking Vytorin to those taking Zocor alone.

But the companies said Friday that the results of the trial, which had been expected in 2011, would not be available until 2012, and possibly later.

As a result, doctors who prescribe the medicines are doing so without hard evidence that they help patients, said Dr. Steven Nissen, chairman of cardiology at the Cleveland Clinic.

Weve got a drug that has no clinical outcome trials, Dr. Nissen said. I advise my colleagues essentially to use this drug only as a last resort.

Dr. John Kastelein, the Dutch cardiologist who conducted the trial, called Enhance, that was discussed at the conference, said the companies must aggressively explore reasons that the trial failed. For example, they need to examine closely whether Zetia blocks the absorption of nutrients other than cholesterol in the intestine, or whether it has other effects on the lining of blood vessel walls.

We can use a lot better science, he said.

The recommendations released Sunday will probably have an immediate impact on clinical practice, said Dr. Douglas Weaver, the incoming president of the American College of Cardiology, which was host of the conference. Nearly half of the 30,000 cardiologists in the United States attend the conference, and many of those doctors heard the panels recommendations firsthand.

I do think that the drugs have been overutilized in this country, Dr. Weaver said. Heavy marketing has probably contributed to that overuse, he added. But use will decline as more patients and doctors focus on the results of the Enhance trial.

Sometimes you have to tell people multiple times before they get the message, he said

From New York Times

New evidence shows that the drug makers Merck and Schering-Plough have conducted several studies of their popular cholesterol medicine Zetia that raise questions about its risks to the liver, but the companies have never published those results.

Partial results of the studies, alluded to in documents on the Food and Drug Administrations Web site, raise questions about whether Zetia can cause liver damage when used long term with other cholesterol drugs called statins.

Most of the millions of people who use Zetia take it along with a statin like Lipitor, Crestor or Zocor. Or they take it in a single pill, Vytorin, that combines Zetia with Zocor.

The discovery of the unpublished research comes as Merck and Schering are already under criticism for not yet releasing data from an important Zetia study, called Enhance, that they completed early last year.

The Enhance data may also contain important information about Zetias liver risks. At least some patients were dropped from the Enhance study after testing revealed that they had elevated liver enzymes, a Schering-Plough spokesman confirmed this week.

But a full report on that trial, including the number of patients who had liver problems, will not be available until March.

Doctors say that by failing to disclose promptly all their research, Merck and Schering-Plough may be leaving the public with a misleadingly favorable view of Zetias safety and benefits.

You dont want to have data missing, said Dr. Bruce Psaty, a professor of medicine and epidemiology at the University of Washington. When there have been adverse effects, when the benefits dont look impressive, those are the trials that historically dont make it to press.

A Schering executive, when asked by a reporter about the unpublished studies, confirmed their existence. But the executive, Dr. Robert J. Spiegel, said the companies had not considered the studies scientifically important enough to publish their findings. Some may eventually be published, he said.

Were pretty comfortable that people dont have trouble tolerating Zetia, said Dr. Spiegel, the chief medical officer of the Schering-Plough Research Institute, Kenilworth, N.J.

Schering also said that the F.D.A. had reviewed the data from the unpublished studies and had approved Zetia for use alongside statins. But experts on drug safety say that the agency has been slow to issue warnings about many widely used drugs that have turned out to carry serious risks, including the painkiller Vioxx, the diabetes medicine Avandia and the anti-psychotic drug Zyprexa.

Even doctors critical of Zetia generally say it is safe for most patients. But before the drug was approved in 2002, one F.D.A. reviewer said it should not be cleared for use with statins because the combination had caused liver damage in animals. And in the last two years, scattered case reports of severe liver damage in patients taking Zetia in combination with statins have appeared in medical journals.

In the United States, the product label for Zetia contains only mild warnings about the drugs potential for liver damage.

But in Australia and Canada, regulators have been more cautious. Since 2005, they have issued a series of warnings about Zetias potential to cause hepatitis, pancreatitis and depression

warnings that have largely gone unnoticed in the United States.

All drugs have potential risks and side effects, of course, and doctors and patients must weigh those against a drugs medical benefits. But in the case of Zetia, despite its widespread use, there is no evidence proving that Zetia can reduce heart attacks and strokes, as cholesterol drugs are meant to do. There is extensive medical evidence showing that Lipitor and other statins provide such protection.

The unpublished Zetia studies, devised as safety tests, would not prove the drugs effectiveness. But they would give the public more information about Zetias potential risks. All the unpublished studies covered periods at least one year in length and were intended to show whether long-term use of Zetia might pose dangers that short-term use did not.

Most of the studies about Zetia in which Merck and Schering have published the results covered periods of only 12 weeks

not enough time for liver problems to develop in most patients.

The unpublished studies, conducted from 2000 to 2003 according to the F.D.A. documents, were not listed on the industry Web sites where companies are supposed to register the results of all drug trials that were ongoing after October 2002. The New York Times discovered references to the studies in briefing papers on the F.D.A. Web site.

We keep telling people we want to practice evidence-based medicine, and what we keep finding out is that much of the evidence is obscured, said Dr. Harlan Krumholz, a cardiologist at Yale, when told about the previously undisclosed studies. There is important evidence, but its not in public view. Its hidden from investigators.

Schering and Merck

which are on track to earn $5 billion this year from sales of Zetia

had already been criticized for not promptly releasing results of the Enhance trial, which was completed in April 2006. Under pressure from Congress and prominent cardiologists, the companies said recently that they would release the full results of the Enhance trial by March.

In response to questions from The Times, the Schering spokesman, Lee Davies, disclosed this week that some patients in the Enhance trial had been dropped from it after tests showed that they had elevated liver enzymes

a potential sign of organ damage. But Mr. Davies said he could not disclose how many, and said the companies did not even know if the patients who had been dropped were taking Zetia and a statin, or just a statin. The delay in releasing the Enhance trial data is unrelated to the patients who were discontinued, Mr. Davies said.

The Enhance data are expected to provide the clearest picture yet of Zetias long-term affects. But the F.D.A.s documents show that Merck and Schering conducted several other long-term trials of Zetia without releasing their findings.

Together those studies cover several thousand patients who took Zetia along with statins for one to two years. The statins include Lipitor and Crestor, as well as Zocor, which is usually prescribed generically as simvastatin and is the statin used in the Vytorin pill. Doctors often add Zetia to a low dosage of a statin, because Zetia reduces cholesterol in a different way than the statins do and leads to deeper overall cholesterol reductions.

One open question is whether Zetias method of lowering cholesterol provides the same medical benefits as fighting cholesterol with a higher-dose statin by itself. Last year, Merck and Schering began a separate study

a 10,000-patient clinical trial to prove that Zetias ability to lower cholesterol will translate into fewer heart attacks and strokes in patients. But data from that trial will not be available until at least 2011.

In the meantime, some doctors say, they must essentially take on faith that Zetias cholesterol-lowering ability will translate into real-world benefits and that its long-term use with statins does not have major risks.

Dr. Eric J. Topol, a cardiologist and director of the Scripps Translational Science Institute in La Jolla, Calif., said that he had asked Merck and Schering more than four years ago to conduct a large, long-term trial to prove that Zetia could reduce heart attacks and strokes. But the companies had little interest, he said.

They looked at me like I was an alien, Dr. Topol said.

Two months ago, President Bush signed a new law intended to strengthen penalties for companies that do not release information promptly. And in 2004, the drug industry promised to improve disclosure of research results.

But the new law applies only to new trials, meaning the unpublished Zetia trials are not covered by those new rules and guidelines.

The F.D.A. has reviewed the unpublished studies, according to the agencys briefing papers.

The companies own published studies have generally played down the risk of liver problems. But Dr. Mark Stolk, a gastroenterologist in the Netherlands, last year reported two cases of patients who had developed hepatitis, a liver disease, after taking Zetia alongside Lipitor. One of the patients has since died, Dr. Stolk said in an interview last month. While Zetia is safe for most patients, doctors should carefully monitor patients for liver damage, he said.

I think other cases will emerge, he said.

When the F.D.A. approved Zetia in 2002, it relied on trials that covered only 3,900 patients and lasted no more than 12 weeks. Still, the data from even those trials contained signals that Zetia might be dangerous in some patients when it is taken alongside statins, as it usually is.

In those trials, 11 times as many people who took Zetia along with a statin subsequently had serious health problems, compared with those who took a statin alone. Nearly all the serious problems were liver-related. Still the F.D.A. regarded the risks as relatively minor and approved Zetia without asking the companies to conduct longer trials.

The agency did not respond to requests for comment.

All drugs have risks, of course. Doctors who prescribe Zetia say that while they would prefer to see long-term trial data, they are comfortable using it because decades of evidence demonstrated that lowering LDL, or so-called bad cholesterol, is good for patients.

But Dr. Beatrice A. Golomb, an associate professor at the University of California, San Diego, said doctors have lost sight of the purpose of prescribing drugs like Zetia.

The goal of prescribing cholesterol-lowering drugs is not reducing cholesterol, Dr. Golomb said. It is reducing the number of deaths and heart attacks in patients, he said. And without data to prove that Zetia actually reduces heart attacks, doctors cannot be sure they are helping patients when they prescribe the drug, she said.

From News - Revolution Health

Previous studies of a link between statins, a cholesterol lowering medication, and cognitive decline have produced mixed results. New research suggests that the relationship between statin use and cognitive decline appears even more complex than originally thought.

The study involved 1,146 African Americans aged 70 and older living in Indianapolis whose cognitive status was assessed in 2001 and again in 2004.

The Indianapolis-based researchers found that cognitive decline in people who took statins was less than in those who did not take statins.

However, those who continued to take statins from 2001 to 2004 had greater cognitive decline than those who were taking statins in 2001 but were no longer taking them in 2004. If statin use were directly associated with a reduction in cognitive decline, continuously taking statins would presumably produce the greatest effect.

“The relationship between statin use and cognitive decline is complex and subjected to unknown confounders,” Dr. Stanley Szwast, of Indiana University School of Medicine, and colleagues note in a report in the journal Neurology. “This effect may not be associated with the cholesterol lowering or anti-inflammatory action of statins.”

“We know that taking statin medication can protect against cardiovascular events such as heart attacks by lowering blood cholesterol. The question at hand is what effects do these medications have on brain function. Our study along with others shows promising results but larger controlled studies are needed,” Szwast noted in a statement.

SOURCE: Neurology, November 6, 2007