The Lipid Research Clinics Coronary Primary Prevention Trial. Results of 6 years of post-trial follow-up. The Lipid Research Clinics Investigators

Abstract

Background: Participants in the Lipid Research Clinics Coronary Primary Prevention Trial, a randomized, cholesterol-lowering trial comparing cholestyramine (N = 1907) vs placebo (N = 1899) treatment in 35- and 59-year-old asymptomatic hypercholesterolemic men, conducted between 1973 and 1983, were followed up annually from 1985 until 1989. Post-trial treatment was not provided.

Methods: Eleven predefined hypotheses pertaining to possible benefits and adverse effects of in-trial cholestyramine treatment were tested by standard statistical comparisons of the two original Coronary Primary Prevention Trial treatment groups (cholestyramine and placebo).

Results: Similar increasing proportions of cholestyramine and placebo used cholesterol-lowering drugs post-trial. After 13.4 years of in-trial plus post-trial follow-up, there were 13 (143 vs 156) fewer deaths in the cholestyramine group than in the placebo group. Although not statistically significant, the mortality hazard ratio (0.89) was similar to that in other cholesterol-lowering trials. This trend, a result of reduced coronary heart disease mortality, occurred despite a post-trial narrowing of the in-trial cholestyramine-placebo difference in coronary heart disease incidence from 32 (155 vs 187) to 16 (268 vs 284). The cholestyramine and placebo groups had similar 13.4-year mortality rates from cancer, other medical causes, and trauma and similar cancer incidence rates. However, 13.4-year incidences of benign colorectal tumors (50 vs 34), cancer of the buccal cavity and pharynx (eight vs two), gallbladder disease (68 vs 53), and gallbladder surgery (58 vs 40) were nonsignificantly increased in the cholestyramine group.

Conclusion: Overall, 6 years of post-Coronary Primary Prevention Trial follow-up have not provided conclusive evidence of benefit or long-term toxicity of cholestyramine treatment beyond that evident at the cessation of the trial.