The Coronary Drug Project was conducted between 1966 and 1975 to assess the long-term efficacy and safety of five lipid-influencing drugs in 8,341 men aged 30 to 64 years with electrocardiogram-documented previous myocardial infarction. The two estrogen regimens and dextrothyroxine were discontinued early because of adverse effects. No evidence of efficacy was found for the clofibrate treatment. Niacin treatment showed modest benefit in decreasing definite nonfatal recurrent myocardial infarction but did not decrease total mortality. With a mean follow-up of 15 years, nearly 9 years after termination of the trial, mortality from all causes in each of the drug groups, except for niacin, was similar to that in the placebo group. Mortality in the niacin group was 11% lower than in the placebo group (52.0 versus 58.2%; p = 0.0004). This late benefit of niacin, occurring after discontinuation of the drug, may be a result of a translation into a mortality benefit over subsequent years of the early favorable effect of niacin in decreasing nonfatal reinfarction or a result of the cholesterol-lowering effect of niacin, or both.

Among elderly persons, a significant and substantial excess risk of death and stroke or myocardial infarction was associated with an increase in depressive symptoms over time, which may be a marker for subsequent major disease events and warrants the attention of physicians to such mood changes. However, further studies of casual pathways are needed before wide-spread screening for depression in clinical practice is to be recommended.

Niacin was one of the treatments compared in the Coronary Drug Project, a placebo-controlled, multicenter trial of lipid-lowering drugs in the secondary prevention of coronary heart disease. A total of 1119 men, aged 30-64 at entry, were randomized to niacin and 2789 to placebo by the end of recruitment in March 1969. Although side-effects interfered with adherence to the niacin regimen, it was the most effective agent in achieving cholesterol-lowering (10% overall); other agents in the trial were clofibrate, dextrothyroxine, and conjugated equine estrogens. At the scheduled conclusion of the trial in February 1975, the niacin-treated group exhibited a statistically significantly lower incidence of definite, non-fatal myocardial infarction (MI) than the placebo group. There was a trend toward improvement in the life-table mortality curve, but this was not statistically significant. In 1981 an extended follow-up was carried out concerning vital status for the 6008 men who were still alive at the end of treatment and active follow-up in the trial in 1975 (827 in the niacin group and 2008 in placebo groups). Vital status was determined for 99.1% of these men after a mean of 9 years from conclusion of the trial. In the group previously randomized to niacin, there were 69 (11%) fewer deaths than were expected on the basis of mortality in the placebo group. This difference was significant (z = -3.52; P = 0.0004). The data also suggested that patients with a higher baseline cholesterol experienced greater benefit from niacin therapy, as did those with the best response to the drug.(ABSTRACT TRUNCATED AT 250 WORDS)

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SUMMARY The Coronary Drug Project was a randomized, placebo-controlled trial of lipid-influencing drugs in men who had recovered from one or more documented myocardial infarctions. Determinations of high-density lipoprotein (HDL) cholesterol were made at baseline in a group of 354 men randomized to the placebo group. Five-year mortality was highest (33.0%) in men with baseline serum HDL cholesterol levels of less than 35 mg/dl; it was 15.9%, 17.7%, and 21.8% in men with levels of 35-39, 40-44, and 45 mg/dl, respectively (for the linear inverse relationship between HDL cholesterol and 5-year mortality, p = 0.029). Adjustment for 40 baseline variables had a minimal effect on this relationship (p = 0.042).

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The effect of atenolol and reserpine on incidence of strokes, coronary heart disease (CHD), cardiovascular disease (CVD), and mortality was assessed in 4736 persons aged 60 years and older with isolated systolic hypertension. Participants were randomized to either chlorthalidone (2371), with step-up to atenolol, or reserpine if needed, or placebo (2365). The average baseline SBP/DBP was 170/77 mm Hg. In the active treatment group, step 1, dose 1 was chlorthalidone, 12.5 mg/day; dose 2 was 25 mg/day. For step 2, dose 1 was atenolol 25 mg/day (or reserpine 0.05 mg/day if atenolol was contraindicated); dose 2 was 50 mg/day (reserpine, 0.10 mg/day). During 4.5 years average follow-up, 32% (757) of the active treatment group were on atenolol, with an average exposure of two years and 8% (193) were on reserpine with an average exposure of 1.7 years. Overall there were 96 strokes, 140 CHD events and 289 CVD events among the 2365 active group participants. Using time-dependent lifetable regression with adjustment for several variables, the addition of either atenolol or reserpine to chlorthalidone did not substantially alter the risk ratios for chlorthalidone alone. The relative risk for CHD events for atenolol versus no atenolol was 1.04 (95% confidence interval: 0.58, 1.86) and for reserpine versus no reserpine was 0.93 (95% confidence interval: 0.29, 2.96). The relative risk for atenolol were 0.84 (95% confidence interval: 0.54, 1.30) for death, 1.34 (95% confidence interval: 0.80, 2.28) for stroke, and 1.07 (95% confidence interval: 0.71, 1.61) for CVD. For reserpine, the corresponding relative risks and confidence intervals were 0.65 (0.26, 1.59) for death, 0.27 (0.04, 2.26) for stroke, and 0.55 (0.20, 1.49) for CVD. Thus, the beneficial effects in several outcomes in Systolic Hypertension in the Elderly Program (SHEP) were due to the treatment regimen of lowering blood pressure based on low-dose chlorthalidone (plus atenolol or reserpine as required to meet blood pressure criteria). Additional (independent) benefits attributable to atenolol or to reserpine were not identified. However, a greater number of patients might have been necessary to adequately evaluate potential differential effects of these drugs, especially for reserpine.

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