Lipid Research Clinics Coronary Primary Prevention Trial (CPPT)
Condition: Cardiovascular Diseases; Coronary Disease; Heart Diseases; Myocardial Ischemia
MeSH terms: Cardiovascular Diseases; Heart Diseases; Coronary Disease; Myocardial Ischemia; Ischemia
Study type: Interventional
Phase: Phase 3

Summary: 
      To determine whether reduction of cholesterol by drug therapy significantly lowered the
      atherosclerotic coronary heart disease rate in a group of hypercholesterolemic but otherwise
      healthy men.

      Total dollars spent on the CPPT from June 1973 were $142,250,000. We do not have a
      year-by-year breakdown.
    

Detailed description: 
      BACKGROUND:

      Numerous prospective epidemiologic studies have demonstrated that hypercholesterolemia is a
      major risk factor for atherosclerotic coronary heart disease. Research on animals indicating
      that the reduction of serum cholesterol prevented or reversed atherosclerosis had not been
      shown convincingly in humans. The Coronary Primary Prevention Trial tested the hypothesis
      that lowering the serum cholesterol in patients who had no existing evidence of coronary
      heart disease would reduce the subsequent rate of coronary heart disease in those persons.

      Coronary heart disease is the leading cause of death and a major cause of morbidity in the
      United States. The very slow development of the underlying arterial disease and its
      frequently sudden onset and quickly fatal course necessitate a preventive approach if
      substantial inroads are to be made. The positive result from the Coronary Primary Prevention
      Trial (CPPT) has done much to resolve the controversy regarding the benefits of
      lipid-lowering, and should lead to firm advice for high-risk hypercholesterolemic subjects
      and for the population as a whole.

      The CPPT was part of the Institute's Lipid Research Clinic Program under the Lipid Metabolism
      Branch, DHVD, NHLBI. Twelve lipid research clinics in the United States and Canada
      participated in this trial, as well as a coordinating center, a central electrocardiographic
      laboratory, central lipid and clinical chemistry laboratories, a nutrition coding center, and
      a group of consultants on recruitment and adherence. This program's objectives included the
      development of standardized methods and definitions for the diagnosis of hyperlipoproteinemia
      and the performance of a series of collaborative studies of the prevalence and natural
      history of this disorder, as well as the design and implementation of the Coronary Primary
      Prevention Trial.

      The protocol for the trial was approved in November 1972. Beginning in July 1973, men with
      hypercholesterolemia were recruited as potential trial subjects from such diverse sources as
      physician referrals, blood bank donor lists, and mass screening programs. Each subject was
      screened further in a series of four visits, the purpose of which was to select only men (1)
      whose lipid abnormality was of the primary Type II phenotype, (2) who were free of clinically
      manifest coronary heart disease, and (3) whose excellent overall health and reliability made
      7-10 years of follow-up a realistic objective. Additionally, a standardized
      limited-cholesterol/saturated fat diet was initiated at the second of these visits in order
      to exclude men whose cholesterol levels were highly responsive to diet. Subjects who met all
      the selection criteria were randomly assigned, in a double-blind fashion, to receive either
      the cholesterol-lowering drug cholestyramine or a placebo at their fifth visit.

      Recruitment of the 3,806 CPPT subjects was completed in July 1976. After randomization into
      the study, each subject visited his clinic at bimonthly intervals. At these visits, adherence
      to drug and diet were assessed, the study medication was supplied, general health and
      potential toxic side effects were monitored, and intervening cardiovascular events were
      recorded. Counseling in drug and dietary adherence were given at each visit, and medical
      advice was given when a problem was identified. Trial data were collected and analyzed at the
      Central Patient Registry and reviewed periodically by a Safety and Data Monitoring Board.
      Intervention ceased between May and August 1983. A five-year follow-up was initiated in
      November 1984 to detect possible toxicity in the CPPT participants following ingestion of
      cholestyramine (or placebo) for 7 to 10 years. Follow-up was completed in October 1989.

      DESIGN NARRATIVE:

      Randomized, double-blind, fixed sample size with one experimental group and one control group
      of equal size. Experimental group on diet and lipid-lowering drug regimen; control group on
      diet and placebo regimen.
    

Intervention name(s): cholestyramine; diet, fat-restricted
Intervention type(s): Drug; Behavioral
Intervention MeSH terms: Cholestyramine Resin
Allocation: Randomized
Masking: Double
Primary purpose: Prevention