Lipid Research Clinics Coronary Primary Prevention Trial - LRC-CPPT


Lipid-lowering for CAD in asymptomatic men with primary hypercholesterolemia.


The lowering of cholesterol (or LDL-C) levels would reduce the incidence of endpoints.

Study Design

Study Design:

Patients Screened: 480,000
Patients Enrolled: 3,806
Mean Follow Up: 7.4 years
Mean Patient Age: 47.8
Female: 0

Patient Populations:

Men aged 35 to 59 years
Plasma cholesterol level >265 mg/dL
LDL-C level >190 mg/dL
Type II hyperlipoproteinemia


Men with triglyceride levels averaging >300 mg/dL
Type III hyperlipoproteinemia
History of definite or suspect MI
Angina pectoris, as determined by Rose Questionnaire
Angina pectoris during exercise ECG
Various ECG abnormalities, according to the Minnesota code-left bundle-branch block, tertiary or secondary heart block, two or more consecutive ventricular premature beats, left ventricular hypertrophy, R-on-T-type ventricular premature beats, or atrial flutter or fibrillation
Congestive heart failure
Conditions associated with secondary hyperlipoproteinemia
Hypertension or receiving antihypertensive medication
Life-limiting or comorbid conditions

Primary Endpoints:

Definite coronary heart disease related death or definite nonfatal MI

Secondary Endpoints:

All-cause mortality
Development of an ischemic response to exercise (positive exercise test result)
Angina pectoris as determined by Rose Questionnaire
Atherothrombotic brain infarction
Arterial peripheral vascular disease (intermittent claudication as determined by Rose Questionnaire)
Transient cerebral ischemic attack

Drug/Procedures Used:

Bile acid sequestrant cholestyramine resin, 24 g/day (six packets per day, divided into two or four equal doses)

Concomitant Medications:

A moderate, cholesterol-lowering diet designed to lower plasma total cholesterol levels by 3-5%, encouraged in all patients

Principal Findings:

With cholestyramine, the mean plasma total cholesterol was reduced by 13.4% and the LDL cholesterol by 20.3%. Compared to placebo, these reductions were 8.5% greater for mean plasma total cholesterol and 12.6% greater for LDL cholesterol) (p>0.001).

The cholestyramine group also had a reduced risk (19%)) p <0.05) of definite coronary heart disease related death or definite nonfatal MI (primary endpoint), which reflected a 24% reduction in definite coronary heart disease death and a 19% reduction in nonfatal MI.

The reduction in mortality from all causes was 7% (p = not significant).

Gastrointestinal side effects were more common with cholestyramine.

In a follow-up substudy of 1899 men, patients with higher serum carotenoid levels had a decreased risk of CHD. This finding was stronger among men who never smoked (adjusted relative risk was 0.28 with a confidence interval of 95%, 0.11 to 0.73).


Cholestyramine treatment was associated with an average cholesterol fall of 8.5% beyond diet, and an average 19% reduction in CHD risk.
A 49% reduction in CHD incidence would be predicted for subjects who obtained a 25% fall in plasma cholesterol levels or a 35% fall in LDL-C levels, which are typical responses to 24 g of cholestyramine resin daily.


1. JAMA 1984;251:351-364. Final results (clinical)
2. JAMA 1984;251:365-374. Final results (lipid levels)
3. Am J Cardiol 1984;54:14C-19C. Study design
4. Am J Cardiol 1984;54:30C-34C. Review
5. JAMA 1994;272:1439-1441. Carotenoid substudy

Clinical Topics: Dyslipidemia, Prevention, Homozygous Familial Hypercholesterolemia, Lipid Metabolism, Nonstatins, Primary Hyperlipidemia, Diet

Keywords: Carotenoids, Cholestyramine Resin, Follow-Up Studies, Hyperlipoproteinemia Type II, Bile Acids and Salts, Diet, Confidence Intervals, Hypercholesterolemia

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