Authors
Lipid Research Clinics Program
Title
Reduction in Incidence of Coronary Heart Disease
References
JAMA. 1984 Jan 20;251(3):351-64
Background
Coronary heart disease (CHD) is a major cause of death and disability in the United States. Observational epidemiologic studies have established that the higher the total or LDL-C level, the greater the risk that CHD will develop. Total and LDL-C levels may be reduced by dietary intervention as well as drugs. Before such treatment can be advocated, it must be concluded that cholesterol plays a causal role in the pathogenesis of CHD and that reducing cholesterol levels reduced the risk of CHD.
Purpose
To test the efficacy of cholesterol lowering in primary prevention of CHD in middle aged men with primary hypercholesterolemia.
Design
  • Double-blind, placebo controlled trial
  • 3806 asymptomatic men aged 40-49 years with an LDL-C of > 4.9 mmol/L (190 mg/dL) were enrolled
  • Divided into 2 equal groups and stratified by risk of CHD as determined by LDL-C levels greater or less than 5.6 mmol (215 mg/dL)
Exclusion Criteria
  • History of definite myocardial infarction
  • Angina pectoris
  • Angina during exercise ECG
  • ECG abnormalities such as LBBB or AV block
  • Congestive heart failure
Follow-Up
Minimum 7 and up to 10 years. Mean 7.4 years
Treatment Regimen
  • Bile acid sequestrant cholestyramine at 24 g/day divided into 2-4 equals doses or an equivalent amount of placebo
  • Both groups followed a moderate cholesterol lowering diet
  • Participants evaluated at clinic every 2 months
  • At annual and/or semi-annual visits, resting and exercise ECGs performed as well as 24-hr dietary recalls
  • LDL-C measured at each visit
Results

Primary Endpoints

  • Combination of definite CHD death and/or definite non-fatal myocardial infarction.
  • The cholestyramine group experienced a 19% reduction in combined endpoint -7% (cholestyramine) vs. 8.6% (placebo) p<0.05. This reflected a 24% reduction in definite CHD death and a 19% reduction in non-fatal myocardial infarction.

Secondary Outcomes

(see study for complete list)

  • All cause mortality (reduced by 7% in cholestyramine group) – p=0.08
  • Development of ischemic changes on exercise ECG (reduced by 25% in cholestyramine group) p=0.01
  • Angina (reduced by 20% in cholestyramine group) p<0.01
  • Peripheral vascular disease (reduced by 15% in cholestyramine group) p>0.1
  • Transient ischemic attack (reduced by 18% in cholestyramine group) p>0.1
Summary
Reducing total cholesterol by lowering LDL-C levels can reduce the incidence of CHD risk (morbidity and mortality) in men. This trial provided strong evidence for a causal role for lipids in the pathogenesis of CHD.