Studies showing benefit from lipid-modifying therapy in patients with established coronary atherosclerosis have confirmed that reducing low-density-lipoprotein (LDL) cholesterol levels may be associated with reduced total and cardiovascular mortality and nonfatal cardiac events. Gemfibrozil was found to reduce the incidence of cardiovascular events in the Helsinki Heart Study. This beneficial result was associated with a gemfibrozil-induced increment of high-density-lipoprotein cholesterol (HDL) levels. Frick and associates conducted a double-blind, randomized study to determine the effectiveness of treatment with gemfibrozil in patients with coronary atherosclerosis who had low HDL levels.

A total of 395 men 70 years of age or younger were randomized to receive either slow-release gemfibrozil in a dosage of 1,200 mg per day or placebo. All patients had previously undergone successful coronary bypass surgery and had HDL cholesterol levels of 1.1 mmol per L (42.5 mg per dL) or less and LDL cholesterol levels of 4.5 mmol per L (174 mg per dL) or less. Coronary angiography was performed at baseline and after 32 months of therapy. Changes in coronary dimensions were assessed by computer-assisted analysis.

From baseline, patients in the gemfibrozil group experienced a 36 percent reduction in triglyceride levels. Total and LDL cholesterol levels were reduced by 5.5 and 4.5 percent, respectively, and HDL cholesterol levels increased by 21 percent from baseline. In the placebo group, triglyceride levels increased 4.6 percent from baseline, total cholesterol increased 5.1 percent, LDL cholesterol levels increased 5.3 percent and HDL cholesterol levels increased by 7.0 percent. The differences between the active treatment group and the placebo group were highly significant.

Diffuse progression of coronary atherosclerosis measured by arteriograms was significantly milder in the gemfibrozil-treated group than in the placebo group in segments unaffected by grafts and in graft-affected segments. By contrast, there was no difference in the average diameter of the segments of the graft-dependent segments in either group. When all types of native coronary segments (unaffected, graft-affected and graft-dependent) were taken into account, there was significantly less progression of focal coronary atherosclerosis in the gemfibrozil group compared with the placebo group.

Progression of focal coronary atherosclerosis was reduced in patients in the gemfibrozil group although the difference was not statistically significant for the primary segment. Expressed as an average per patient change in percent diameter stenosis, lesion progression was milder in the gemfibrozil group when compared with the placebo group, but the differences were not statistically significant. The appearance of new lesions in primary segments did not show a significant difference between the two groups. There was a marked reduction with active treatment in the number of new lesions in the venous aortocoronary bypass grafts.

The authors conclude that the results of this study demonstrate that therapy with gemfibrozil retards angiographic progression of coronary and vein-graft atherosclerosis in a group of post-coronary bypass men selected on the basis of low HDL cholesterol levels at baseline. The data found here support the conclusions of other large trials that active treatment of dyslipidemias after bypass surgery retards the progression of atherosclerosis both in native coronary arteries and in bypass grafts.

The authors conclude that in patients with low HDL cholesterol but normal or only mildly elevated LDL cholesterol levels, reducing the atherogenic remnants of triglyceride-rich lipoproteins and increasing levels of antiatherogenic HDL cholesterol retards the progression of coronary artery disease.