November 2001

From University of Washington

Treatment reduces risk of heart attack by 60 to 90 percent, reverses arterial plaque buildup; antioxidant vitamins diminish beneficial effect

Treatment with a combination of statin and niacin can slash the risk of a fatal or non-fatal heart attack or hospitalization for chest pain by 70 percent among patients who are likely to suffer heart attacks and/or death from coronary heart disease, according to a study by University of Washington researchers in the Nov. 29 New England Journal of Medicine.

Cardiovascular disease is the No. 1 killer in most industrialized countries.

The study also found that a mixture of antioxidant vitamins had no beneficial effect on cardiovascular outcomes.

The treatment that cut the risk for cardiovascular events combines two well-known ways of improving cardiac health: the use of a statin drug to lower levels of the "bad" cholesterol, LDL, and the use of niacin to boost levels of the "good" cholesterol, HDL. The study found that use of this combined treatment, in people with low levels of "good" HDL and average levels of "bad" LDL, could even reverse plaque buildup in the arteries.

At the start of the study and again after three years of treatment, doctors performed angiograms of the patients' arteries. The angiograms, using computerized measurements, showed that in most of the patients who received the combination treatment, plaque buildup had actually decreased.

"This is the first demonstration of a striking clinical benefit from this form of combination drug therapy used in patients with a common type of coronary disease," said Dr. B. Greg Brown, lead author of the study, a cardiologist and UW professor of medicine.

The study was funded by the National Heart, Lung, and Blood Institute (NHLBI).

"This study shows that improving cholesterol levels in people with heart disease --especially lowering LDL "bad" cholesterol substantially, together with raising HDL "good" cholesterol -- greatly reduces the risk for a heart attack and heart disease complications and can actually reverse the buildup of cholesterol in the arteries of the heart," said Dr. Claude Lenfant, director of the National Heart, Lung, and Blood Institute.

"The study also contributes to the evidence that antioxidant vitamins may not be beneficial in the treatment of heart disease."

The study found that a mixture of antioxidant vitamins blunted the expected rise in the "good" HDL cholesterol usually seen with the simvastatin and niacin combination. Scientists are not sure why this is so, since there has been laboratory evidence that suggests antioxidants should be helpful.

However, the recent "Heart Protection Study" from the United Kingdom confirmed the lack of benefit from the vitamin combination. The study had included antioxidants because there has been considerable evidence that they should help protect against the basic mechanisms for cholesterol buildup. The antioxidants involved in this study include Vitamins C, E, beta carotene and selenium.

Brown was director of the first study in the late 1980s that showed that a member of the statin class, lovastatin, could cause improvement in arterial blockage and reduce the occurrence of major cardiovascular events. Giving statins to people with cardiovascular disease is now common, and has been proven to reduce cardiovascular risk by 25 to 35 percent over five years of treatment.

Brown and colleagues had surmised that combining simvastatin with niacin might more effectively prevent heart attacks and the need for procedures such as coronary bypass. The goal would be to reduce plaque buildup. That's important because the growth of cholesterol-rich plaque blocks blood flow and can lead to fatal complications.

"What is expected with statins is a slowing of the disease progression, but not a reversal. Arteries continue to get narrower, but not as fast," Brown said. "But when niacin is combined with a statin, the artery blockage actually improves a bit, on average."

The statins lower blood levels of LDL, which is called the "bad" cholesterol because it contributes to plaque growth and arterial blockage. HDL, on the other hand, helps protect against heart disease. Niacin, or Vitamin B3, is the best agent known to raise blood levels of HDL, which helps remove cholesterol deposits from the artery walls.

The 160 patients involved in the study had low levels of HDL cholesterol (a level of 35 mg/dl or less). At least four out of every 10 people with coronary artery disease fit this profile.

Some patients in this study received simvastatin and niacin, while others received antioxidants. A third group received all these treatments, while a control group received placebos. All patients received exercise training, as well as anti-smoking and dietary counseling.

The results for those receiving statin and niacin were startlingly different from control patients. The average level of HDL increased from 31 to 39, or 26 percent, while the average LDL dropped from 125 to 76 (down 43 percent) -- that is considered an extremely good level of the bad cholesterol.

Angiograms showed that most of these people had no additional plaque buildup over the years. In many of them, the amount of plaque actually decreased.

"What we saw was a reversal of the disease," Brown said. "The patients' arteries, on average, had stopped narrowing and begun to improve somewhat. Those receiving this lipid therapy combination had 60 to 90 percent fewer major cardiovascular events than the control group."

For the patients receiving antioxidants, the progressive narrowing of the arteries and frequency of major cardiovascular events did not differ from the control patients. And those receiving lipid therapy and antioxidants had less favorable outcomes than the group that had simvastatin and niacin alone. This was due to the observed blunting of the HDL response. The study concludes that niacin adds substantially to the already proven simvastatin benefit, and that the use of antioxidant vitamins to prevent heart disease should be questioned.

The study involved use of niacin at moderately high and carefully supervised levels. Brown said that patients should only take niacin under a doctor's supervision, because in some patients, the doctor may wish to monitor the patient's liver function. Rarely, the unsupervised use of niacin can cause severe liver problems, including liver failure.

Others involved in the study include UW researchers Dr. John Albers, Dr. Xue-Qiao Zhao, Dr. Alan Chait, Dr. Lloyd Fisher, Alice Dowdy, Dr. Marian Cheung, Josiah Morse, Leny Serafini and Ellen Huss-Frechette, as well as Debbie DeAngelis and Dr. Jiri Frohlich of the University of British Columbia, Vancouver, B.C.












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