The Lipid Research Clinics Coronary Primary Prevention Trial: design, results, and implications

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Abstract
The Coronary Primary Prevention Tiral (CPPT) was the major clinical investigation conducted in the Lipid Research Clinics (LRC) Program. There were 12 North American clinics involved in this joint double-blind protocol. The hypothesis tested was: lowering plasma cholesterol in middle-aged men with primary hypercholesterolemia [plasma total cholesterol greater than or equal to 265 mg/dl (6.88 mm/1)] who are otherwise healthy leads to a reduction in coronary heart disease (CHD) as manifest by a reduction in definite myocardial infarction (fatal and nonfatal) over a 7-year follow-up of all participants. The trial was conducted in 3806 male volunteers between the ages of 35 and 59, who were randomly assigned to two equal groups. The treatment group received a moderate cholesterol-lowering diet plus cholestyramine; the placebo group received an identical diet plus a placebo. The study medication was administered at 24 g daily in divided doses. The participants were followed up bimonthly for an average of 7.4 years. The diet (daily cholesterol intake of about 400 mg and a polyunsaturated fat/saturated fat ratio of 0.8) lowered plasma cholesterol by an average of 4%, as designed. The cholestyramine group experienced average plasma total cholesterol (TC) lowering and plasma low-density lipoprotein cholesterol (LDC-C) lowering 8.5% and 12.6% greater than the placebo group, respectively. This resulted in a 19% reduction in definite myocardial infarction (P < 0.05). The trial results for CHD deaths, nonfatal myocardial infarction, new positive exercise stress tests (P < 0.001) new-onset angina (P < 0.01) and coronary artery bypass surgery (P < 0.06) were consistent with and supportive of the main findings of the study. Total mortality also showed a slight decrease in the active treatment group, but the magnitude of the effect was reduced by a greater number of deaths from accidents and violence in the placebo group. The main findings of the study show that the reduction of plasma TC by lowering plasma LDL-C levels can diminish the incidence of CHD morbidity and mortality in men at high risk of CHD. A causal role for these lipids and lipoproteins in the pathogenesis of CHD is strongly suggested. The findings from this and other trials and epidemiologic studies suggest that for every 1% reduction in TC there is a 2% reduction in risk of CHD. The study cohort remains in long-term follow-up.