Many consumers take antioxidant supplements in an effort to ward off heart disease, but a recent study, published in the New England Journal of Medicine, calls into question their effectiveness for this use. Researchers compared a treatment of simvastatin (Zocor) plus niacin with a treatment of antioxidant nutrients in patients with coronary disease. While the simvastatin-niacin treatment was shown to have significant benefit, the antioxidant treatment was not, and may have even blunted the beneficial effects of the simvastatin-niacin treatment in patients who took both.

Statin-niacin associated with fewer cardiac events

One hundred and sixty patients with coronary disease (defined as previous myocardial infarction, coronary interventions, or confirmed angina), low HDL cholesterol levels, and normal LDL cholesterol levels were randomly assigned to one of four treatment regimens: simvastatin (Zocor) plus niacin; antioxidants (800 IU vitamin E, 1000 mg vitamin C, 25 mg beta-carotene, and 100 µg selenium); simvastatin-niacin plus antioxidants; or placebo. The study was double-blind and patients were followed for three years. The composite primary endpoint studied included death from coronary causes, confirmed heart attack or stroke, or revascularization for worsening ischemic symptoms. Changes in lipid levels and in the severity of stenosis were also evaluated.

The risk of the composite primary endpoint was 90% lower in the simvastatin-niacin group than in the placebo group (p=0.03). The risk in the other groups did not differ significantly from the placebo group.

Arteriographic and lipid changes

Patients in the simvastatin-niacin group also experienced a slight regression of existing stenosis (decrease of 0.4% compared with placebo group, p<0.001). In addition, these patients experienced a 65% increase in their levels of HDL-2 (considered the most protective component of HDL) compared with the placebo group. Conversely, antioxidants lowered HDL-2 by 15% (p=0.05 compared with the placebo group) and seemed to blunt the HDL-2-raising effect of simvastatin-niacin when combined with them.

Potential "dual" benefit of statin-plus-niacin

The researchers theorize that patients with low HDL levels who take statin drugs may benefit from a "dual therapeutic pathway": an LDL-lowering effect of statins and an HDL-boosting effect of niacin. On the other hand, their results, in the absence of more compelling evidence, show "little justification for the use of antioxidant vitamins for the prevention of cardiovascular events."

Usefulness of antioxidants still can't be ruled out

However, as discussed in an accompanying editorial, the results of this study alone do not rule out the potential use of antioxidants to prevent coronary heart disease. One important weakness of this study is that it tested a combination of antioxidants, making it impossible to determine the potential effectiveness of any one nutrient.

It is also important to note that the study participants already had coronary disease, as well as low HDL cholesterol levels; therefore, the results do not speak to the potential effectiveness of preventing coronary disease in people who don't have it yet.

While further research is necessary, it may be advisable to consider adding niacin to statin therapy in patients for whom it is indicated, and, of course, to continue to recommend eating a diet rich in antioxidant-containing foods.