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Coronary Drug Project (CDP)

The Coronary Drug Project—findings with regard to estrogen, dextrothyroxine, clofibrate and niacin. (1977) Adv. Exp. Med. Biol. 82: 52-75.

Type Diet/Drug (Stage): Diet (2º)
Study Category: The Prevention Trials (1946-1973)
Year Begun: 1966
Location: United States
Principal Investigator(s): Coronary Drug Project Research Group (Stamler, J. chariman)
External Resource: View URL

Background:

The CDP was one of the earlier randomized clinical trials (RCT) in coronary heart disease (CHD) prevention; it addressed events in men post-myocardial infarction using 5 drugs known to influence blood lipids: 2 dosage groups of estrogens, dextrothyroxine, clofibrate, nicotinic acid, and placebo, and was carried out in 53 clinical centers in the U.S. from 1967 to 1975, supported by NIH.

Methods/Population:

8,341 men, ages 30-64, meeting criteria for recovery from infarcts, were randomly assigned to the 5 drugs or placebo in a double-blinded trial with a detailed common protocol; all were followed for at least 5 years. Quality control was assured by a central laboratory and central ECG Center, a Coordinating Center in Baltimore, and Steering and Data Monitoring, Advisory, and other committees. Visits occurred at four month intervals for lipid level, toxicity, and adherence monitoring. Type I error was set at .01; Type II at .05, to detect a 25 percent reduction in risk.

Results:

Adherence was excellent and cholesterol and triglyceride estimates were achieved. Estrogens and thyroid were stopped early due to trends toward an adverse effect. Clofibrate produced no significant lowering effect on CHD or total mortality during the design period; rather a slight excess of CVD events and major excess of gallstones occurred. Niacin had a small but significant protective effect on non-fatal infarction. Late follow-up after 15 years showed that Niacin had substantially reduced long term risk of CVD and total mortality, in subgroups with and without “metabolic syndrome.”

Conclusions:

Despite the fairly uniform negative early results of this trial, it was a major landmark in the history of prevention research. The CDP indicated the feasibility of such a multicenter undertaking and became a model for trial design, organization, and quality control. Its leadership was effective, inspired, scholarly, and relaxed; coordination was close and supportive; participation was positive and satisfactions were great at all levels. Useful ancillary studies were completed and many monographs and reports emerged over the years from the treated and the placebo groups. CDP demonstrated how a trial could best be managed, a model not always followed among subsequent large multicenter trials. It strengthened the infrastructure of RCT nationally. The CDP was pioneering, useful—and fun! (HB)

References

Stamler, J. “The Coronary Drug Project. Findings with Regard to Estrogen, Dextrothyroxine, Clofibrate, and Niacin.1977. Advances in Experimental Medicine and Biology 82: 52-75

Canner PL, Berge KG, Wenger NK, Stamler J, Friedman L, Prineas RJ, Friedewald W, for the Coronary Drug Project Research Group. “Fifteen-year mortality in Coronary Drug Project patients: long-term benefit with niacin.” (1986) Journal of American College of Cardiology, 8: 1245-1255.