Objectives

The Lipid Research Clinics Coronary Primary Prevention Trial (LRC-CPPT), was a multicenter, randomized, double-blind study, designed to test the efficacy of cholesterol lowering in reducing risk of coronary heart disease (CHD). Selected patients included 3,806 middle-aged men without clinically manifest coronary disease and with primary hypercholesterolemia (type II hyperlipoproteinemia).

Background

At the time of the LRC-CPPT study (enrollment began in 1973), cholesterol had been identified as a major risk factor for coronary heart disease. However, there was only limited evidence that reducing total cholesterol by lowering LDL-C levels could diminish the incidence of CHD morbidity and mortality in men at high risk for CHD. This clinical trial sought to provide evidence for a causal role for these lipids in the pathogenesis of CHD.

Participants

3,806 asymptomatic middle-aged men with primary hypercholesterolemia (type II hyperlipoproteinemia) were tested for the efficacy of cholesterol lowering in reducing risk of coronary heart disease (CHD). The treatment group received the bile acid sequestrant cholestyramine resin and the control group received a placebo for an average of 7.4 years. Both groups followed a moderate cholesterol-lowering diet. The cholestyramine group experienced average plasma total and low-density lipoprotein cholesterol (LDL-C) reductions of 13.4% and 20.3%, respectively, which were 8.5% and 12.6% greater reductions than those obtained in the placebo group. The cholestyramine group experienced a 19% reduction in risk (p less than .05) of the primary end point--definite CHD death and/or definite nonfatal myocardial infarction--reflecting a 24% reduction in definite CHD death and a 19% reduction in nonfatal myocardial infarction. The cumulative seven-year incidence of the primary end point was 7% in the cholestyramine group v 8.6% in the placebo group.

Conclusions

The LRC-CPPT findings showed that reducing total cholesterol by lowering LDL-C levels can diminish the incidence of CHD morbidity and mortality in men at high risk for CHD because of raised LDL-C levels. This clinical trial provided strong evidence for a causal role for these lipids in the pathogenesis of CHD (JAMA, 251(3), 351-64 (January 20, 1984).

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