Coronary drug project: Experience with niacin

Summary

Niacin was one of the treatments compared in the Coronary Drug Project, a placebo-controlled, multicenter trial of lipid-lowering drugs in the secondary prevention of coronary heart disease. A total of 1119 men, aged 30–64 at entry, were randomized to niacin and 2789 to placebo by the end of recruitment in March 1969. Although side-effects interfered with adherence to the niacin regimen, it was the most effective agent in achieving cholesterol-lowering (10% overall); other agents in the trial were clofibrate, dextrothyroxine, and conjugated equine estrogens. At the scheduled conclusion of the trial in February 1975, the niacin-treated group exhibited a statistically significantly lower incidence of definite, non-fatal myocardial infarction (MI) than the placebo group. There was a trend toward improvement in the life-table mortality curve, but this was not statistically significant. In 1981 an extended follow-up was carried out concerning vital status for the 6008 men who were still alive at the end of treatment and active follow-up in the trial in 1975 (827 in the niacin group and 2008 in placebo groups). Vital status was determined for 99.1% of these men after a mean of 9 years from conclusion of the trial. In the group previously randomized to niacin, there were 69 (11%) fewer deaths than were expected on the basis of mortality in the placebo group. This difference was significant (z = - 3.52;P = 0.0004). The data also suggested that patients with a higher baseline cholesterol experienced greater benefit from niacin therapy, as did those with the best response to the drug. No such efficacy was noted in the other regimens, although the two estrogen groups and dextrothyroxine were discontinued before completion of the trial because of adverse effects. The extended follow-up did not provide data on the use of lipid-lowering agents or other treatment in members of either the niacin or the placebo group subsequent to 1975. It was concluded that the late benefit in the niacin group may have been the result of earlier benefit in reducing nonfatal reinfarction, the result of cholesterol lowering, or both.