University of Minnesota

Lipid Research Clinics (LRC) Coronary Primary Prevention Trial

Type Diet/Drug (Stage): Drug (1º)
Study Category: The Prevention Trials (1946-1973)
Year Begun: 1973
Location: United States of America
Principal Investigator(s): Lipid Research Clinics Program


The LRC CPPT was an National Heart Lung and Blood Institute (NHLBI)-sponsored trial to test the hypothesis that long-term reduction of serum cholesterol in hypercholesterolemic men free of clinical coronary heart disease (CHD), would lead to a lowered incidence of CHD. Beforehand, the hypothesis was not accepted by much of the scientific community based on trials and observational studies done prior to this classic undertaking.


A total of 3810 men were enrolled from 12 North American clinics, assigned a standard “prudent diet,” and half randomized to 24 gr/day of a bile acid sequestrant, cholestyramine, half to a placebo. They were followed 7 and again after 13 years for fatal and non-fatal coronary events by a Safety and Data Monitoring Board for adherence, benefit, and adverse effects.


In the ‘classic’ report of 1984, the cumulative 7-year CHD incidence was 7 vs. 8.6 percent with 20 to 25 percent reduction in endpoints of bypass surgery, angina, and positive exercise tests, considered significant with a one-sided test for the main hypothesis. The 13-year follow-up provided inconclusive evidence of sustained benefit or long-term toxicity of Cholestyramine cholesterol-lowering. A 19 percent reduction of CHD risk was associated with an 8 percent reduction in total serum cholesterol or an 11 percent fall in LDL cholesterol. The main effect was from LDL reduction rather than HDL increase.


Despite the small difference found and the one-sided statistical testing, the trial was widely considered a definitive test of cholesterol lowering from which the “two for one” idea derived; that is, 2 percent lowered coronary risk for 1 percent lowered cholesterol level. It was fortunate that the Ileal By-pass trial and the Statin trials came along shortly to produce more clear and dramatic CHD risk lowering with more substantial evidence of safety. (HB)


The Lipid Research Clinics Coronary Primary Prevention Trial Results. I.
Reduction in Incidence of Coronary Heart Disease. JAMA 1984. 251:351-364

The Lipid Research Clinics Coronary Primary Prevention Trial Results. II. The Relationship of Reduction in Incidence of Coronary Heart Disease to Cholesterol Lowering. JAMA 1984; 251:365-374

Results of 6 Years of Post-Trial Follow-up. Arch.Int.Med.1992;152:1399-1410