Posted Nov 20, 2009
More than 70 years ago, researchers at the University of Wisconsin were the first to use niacin, or vitamin B3, as a drug when they found it could quickly cure a horrible disease known as pellagra that began as a skin rash and led to dementia, killing thousands of people every year in rural America.
Another chapter in the saga of niacin was written Monday when new research showed that it outperformed a popular cholesterol-lowering drug in improving artery health.
The research may lead to more use of the reliable stand-by as doctors move toward a different strategy in the fight against heart disease — raising HDL cholesterol (the good kind) instead of just focusing on lowering LDL cholesterol (the bad kind). That’s because heart attacks and strokes still occur even among people whose LDL cholesterol is being controlled with cholesterol-lowering drugs.
“Doctors are faced with an array of options,” said lead author Allen Taylor, a cardiologist at Washington Hospital Center in Washington, D.C. “It is really clear that niacin was superior.”
High-dose niacin performed so well that the trial was stopped early after 14 months based on the results with 208 patients with known heart disease or who were at high risk for heart disease.
The clinical trial involved a comparison of prescription, time-release niacin against the drug ezetimibe (Zetia), which lowers LDL cholesterol by preventing it from being absorbed in the intestines.
In those who got niacin, there was a significant reduction in plaque build up in the carotid artery as measured by ultrasound, which is a surrogate for measuring numbers of heart attacks and strokes. No such artery benefit was found with Zetia.
HDL cholesterol helps prevent heart disease because it removes cholesterol from inside arteries.
Niacin raised HDL cholesterol about eight points whereas Zetia lowered it by three points. Niacin also lowered LDL cholesterol 10 points, compared with a reduction of 18 points with Zetia.
There also were fewer heart attacks and heart-related deaths in the niacin users, although the numbers were small and that benefit was not the major issue studied in the trial.
The study left some important questions unanswered: Was the niacin benefit caused by its HDL-raising ability, its LDL lowering or some other effect? Or was it the result of some unknown bad effect caused by Zetia?
In 2008, 9 million Americans were taking Zetia, although the drug has never been shown to reduce heart attacks or strokes. About 2.5 million people were on prescription niacin.
The study is another piece of bad news for Zetia and its makers, Merck and Schering-Plough, which also market the related drug Vytorin.
Vytorin combines Zetia and simvastatin (Zocor), two drugs that work in different ways to lower cholesterol. In 2008, clinical trial results showed that while the combined drug Vytorin reduced cholesterol about 17% more than just Zocor, there was no significant difference in the plaque thickness found in the carotid arteries of the 720 patients in the trial. In other words, Vytorin did no more for artery health than Zocor alone.
At the time, U.S. Sen. Charles Grassley (R-Iowa) raised questions about whether the trial’s results were delayed for up to two years while the drug maker could institute a marketing campaign designed to switch patients from cheaper statin drugs to the more expensive Vytorin.
In a letter last week, Grassley asked Kathleen Sebelius, secretary of the Department of Health and Human Services, what action she will be taking regarding Medicare payments for Vytorin prescriptions.
Another question on the latest study is whether large numbers of patients tolerate the skin flushing side effect caused by niacin. It can be controlled somewhat by taking aspirin. In addition, new formulations of niacin that reduce flushing are available or are in development.
The study was funded by Abbott, which makes a prescription niacin product. It was published online Monday in the New England Journal of Medicine and presented at the American Heart Association annual meeting in Orlando.
The study suggests that raising HDL is as important as lowering LDL if the patients already are on a cholesterol-lowering drug, said Michael Cinquegrani, a professor of medicine at the Medical College of Wisconsin.
“It (the study) is very provocative,” he said.
Cinquegrani, who already uses niacin in some patients, said the study may prompt him to use it more, especially in those who have low HDL cholesterol.
Zetia is an attractive drug because it is well tolerated, he said, but he would prefer to raise HDL cholesterol.
The study emphasizes that lowering LDL cholesterol should not be the sole strategy for people at high risk for heart disease, said James Stein, a professor of cardiovascular medicine at the University of Wisconsin School of Medicine and Public Health.
The reduction in artery plaque was large, suggesting that niacin also reduces heart attacks and strokes, he said.
“Niacin is the next best drug to add to a statin,” Stein said. “It has a wealth of evidence for preventing cardiovascular events and delaying progression of atherosclerosis. It has earned its place as second in line therapy after high doses of statins.”
Attaining that status was a long journey.
In the first half of the 20th century the disease pellagra was killing tens of thousands of people in the U.S because their diets were deficient in niacin.
In 1937, Conrad Elevhjem, a UW scientist, found that niacin cured pellagra, which, in animals, was known as black tongue.
In the 1950s, other scientists tried to use niacin to treat schizophrenia and while it didn’t work, a surprising side effect was a substantial improvement in cholesterol levels.
By the 1970s doctors were discovering that niacin could reduce heart attacks.
Date: Nov 18, 2009
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