Abbott's Niaspan beats Merck's Zetia in study

Boosting artery-clearing good cholesterol with Abbott Laboratories' Niaspan worked better at opening clogged vessels than reducing bad cholesterol with Merck & Co.'s Zetia, researchers said.

In the study, reported at the American Heart Association meeting in Orlando, Florida, patients given Niaspan had a reduction in artery wall thickness, while those on Zetia had no change. Artery thickness is believed to be a predictor of the risk of heart attack and stroke because too-narrow arteries restrict blood flow, the researchers said.

The finding may raise doctor awareness of the role that boosting good cholesterol, or HDL, has in heart health. It could also erode sales of Merck's Zetia and Vytorin, which combines Zetia with the statin simvastatin to lower bad cholesterol, or LDL. Revenue from the two cholesterol drugs could fall 20 percent, or $800 million, said Seamus Fernandez, an analyst with Leerink Swann & Co. in a note to investors last week.

"We're answering a simple question that clinicians need to know the answer to in order to take better care of their patients," said Allen Taylor, a cardiologist at Washington Hospital Center in the District of Columbia and the study's lead author, in a telephone interview. "The trial results are ultra- clear, Niaspan worked better than Zetia and, through that hopefully, patients are going to benefit."

Third Negative Finding

The negative result is the third in two years for Zetia and Vytorin, and sales have dropped 14 percent to about $3 billion this year.

Merck, located in Whitehouse Station, New Jersey, rose 12 cents to $33.10 in New York Stock Exchange composite trading on Nov. 13, and has risen 21 percent in 2009. Abbott, of Abbott Park, Illinois, fell 28 cents to $52.95. It has declined 4 percent for the year.

In the study, called Arbiter-6 Halts and funded by Abbott, researchers measured the thickness of the neck artery leading to the brain in 208 patients. They were given simvastatin along with either Niaspan, a modified form of vitamin B also known as niacin, or Zetia over 14 months.

The study only looked at patients who had already lowered their LDL cholesterol to the recommended level of 100 milligrams per deciliter of blood or less using a statin.

Even with statins, which recorded $34 billion in worldwide sales last year, patients are having heart attacks and strokes, so doctors continue to seek additional treatments, said Richard Karas, a professor of medicine at Tufts University medical school in Boston, in a telephone interview. Previous studies suggest that HDL-raising drugs could double the benefit of lowering bad cholesterol, he said.

Doctor View

Steven Nissen, chief of cardiology at the Cleveland Clinic in Ohio, said in an interview that the finding may increase use of Niaspan and discourage use of Zetia and Vytorin.

"Yes it is a small study, yes it isn't a substitute for a large definitive outcomes trial, but I do think it will get attention and I do think it will inform us about the choices we have about what therapies we should administer," Nissen said. "There are issues with niacin, some people get flushing, but we are talking about a lethal disease, and I do think there will be an up tick in the use of niacin because of this. It was quiet a compelling result."

Roger Blumenthal, a professor of cardiology at Johns Hopkins University in Baltimore, disagreed in an editorial released by the New England Journal of Medicine. Doctors shouldn't draw definitive conclusions from the study, he said, because it involved a small number of patients and used a secondary measurement, artery thickness, rather than gauging the total number of heart attacks and strokes.

The benefits of Niaspan may also be exaggerated because the study was ended early, Blumenthal said.

Merck Response

Ken Frazier, Merck's president of global human health also said doctors shouldn't change how they treat patients based on the findings.

"Looking at this study, it isn't large or long enough to draw broad conclusions," said Frazier in a Nov. 15 interview. "If people stop lowering LDL there are going to be deaths, that is a fact."

Taylor, the study researcher, said he ended the trial about four months sooner than expected when it became clear that Niaspan had significantly outperformed Zetia.

It wouldn't have been in the patients' best interest to keep the trial going, Taylor said. The study was able to reach a conclusion with fewer patients and over a shorter time period than first thought because the technology being used was more precise than expected, he said.

Heart disease, the build up of fatty plaque in the arteries, killed 445,687 people in 2005 and is the leading cause of death in the U.S., according to the American Heart Association.

Death Rate Decline

With the introduction of statins and procedures to reopen arteries, the death rate from heart disease declined 34.3 percent between 2005 and 1995 in the U.S., though 1.26 million Americans will have a heart attack this year, according to the heart association.

One approach to cutting the number of heart attacks has been trying to lower the LDL as much as possible by increasing the dosage of a statin, or using Zetia, which is designed to work in the digestive tract by stopping the absorption of cholesterol from food.

Niaspan, by contrast, works by raising levels of high- density lipoprotein, or HDL cholesterol, believed to protect against heart attacks by collecting excess artery-clogging LDL cholesterol in the blood and taking it to the liver where it can be disposed.

HDL may also provide a protective benefit to the heart and blood vessels through its antioxidants, anti-inflammatory and anti-clotting effects, according to the Mayo Clinic.

$786 Million in Sales

Using Niaspan, with $786 million in sales last year, to raise HDL has been limited because the drug can cause facial flushing. Merck is testing a form of niacin in combination with an experimental drug laropiprant and will seek U.S. regulatory approval for the medicine as early as 2010.

"If Niaspan is superior to Zetia in the study, we expect the data to provide the Niaspan franchise with a shot in the arm especially if there are significantly fewer events in the Niaspan group," said Larry Biegelsen, an analyst with Wells Fargo Advisors LLC in New York, in a note to investors on Oct. 26, before the study's finding were reported.

Zetia and its combination-version Vytorin have been spurned by doctors over the past two years after a study called Enhance, that used a similar artery-imaging method as in the Arbiter study, found it worked no better than taking simvastatin alone, which costs 77 percent less.

Additional Studies

Another study called Seas, linked the drug to an increase risk of cancer, though a separate analysis found no such link. The number of prescriptions written for the two drugs in the U.S. has declined by 46 percent since the Enhance results were released in January 2008.

There are no studies that have shown that Zetia reduces the risk of heart attacks and stroke. Merck is currently working on one such study involving 18,000 patients. The results won't be available until 2012, a decade after the drug came on the market.

The Arbiter study released today wasn't large or long enough to detect a significant difference in the rates of heart attacks and strokes, said Taylor, the study author.

Though the research found that 5 percent of patients taking Zetia had a heart attack or stroke compared with 1 percent on Niaspan, that finding is not definitive because of the limited size of the study, Taylor said.

Facial Flushing

Patients taking Niaspan were more likely to drop out of the study because of side effects, the study showed. About a third of Niaspan patients said they experienced facial flushing.

Zetia and Vytorin have been shown to lower levels of LDL cholesterol better than statins alone and doctors should focus on getting their patients' LDL cholesterol to the levels recommended by the American Heart Association, said Merck's head of research Peter Kim said in an interview.

"Lowering LDL is an extremely well validated step toward improving cardiovascular health," Kim said. "Numerous studies have shown, if you lower LDL you decrease cardiovascular risk and save lives."