In a randomized, double-blind five-year trial, we tested the efficacy of simultaneously elevating serum levels of high-density lipoprotein (HDL) cholesterol and lowering levels of non-HDL cholesterol with gemfibrozil in reducing the risk of coronary heart disease in 4081 asymptomatic middle-aged men (40 to 55 years of age) with primary dyslipidemia (non-HDL cholesterol greater than or equal to 200 mg per deciliter [5.2 mmol per liter] in two consecutive pretreatment measurements). One group (2051 men) received 600 mg of gemfibrozil twice daily, and the other (2030 men) received placebo. Gemfibrozil caused a marked increase in HDL cholesterol and persistent reductions in serum levels of total, low-density lipoprotein (LDL), and non-HDL cholesterol and triglycerides. There were minimal changes in serum lipid levels in the placebo group. The cumulative rate of cardiac end points at five years was 27.3 per 1,000 in the gemfibrozil group and 41.4 per 1,000 in the placebo group--a reduction of 34.0 percent in the incidence of coronary heart disease (95 percent confidence interval, 8.2 to 52.6; P less than 0.02; two-tailed test). The decline in incidence in the gemfibrozil group became evident in the second year and continued throughout the study. There was no difference between the groups in the total death rate, nor did the treatment influence the cancer rates. The results are in accord with two previous trials with different pharmacologic agents and indicate that modification of lipoprotein levels with gemfibrozil reduces the incidence of coronary heart disease in men with dyslipidemia.

In the Helsinki Heart Study, a randomized five-year, double-blind trial, a 34% reduction in the incidence of coronary heart disease (CHD) was observed in dyslipidemic men treated with gemfibrozil. Averaged over the five years of the trial, gemfibrozil therapy produced, compared with placebo, mean decreases of 10% in serum total cholesterol level, 14% in non-high-density lipoprotein (HDL) cholesterol level, 11% in low-density lipoprotein (LDL) cholesterol level, 35% in triglyceride level, and a mean increase of 11% in HDL cholesterol level from baseline levels measured prior to treatment. While changes in HDL cholesterol level were similar in all Fredrickson types, the effect on concentrations of total cholesterol and LDL cholesterol was largest in type IIA and on LDL minimal in type IV. The reduction of CHD incidence over placebo was largest in type IIB and smallest in type IIA. The lipid changes were dependent on lipid levels prior to treatment and on compliance with the medication regimen. When risk factors for CHD, including age, blood pressure, smoking and drinking habits, baseline lipid levels, and exercise and relative weight, were controlled by applying the Cox proportional hazards model, the changes in serum HDL and LDL cholesterol levels were both statistically significantly associated with the decline in CHD incidence within the gemfibrozil-treated group. The large decrease in serum triglyceride levels had relatively small effect on CHD incidence. Thus, the results of this study, together with earlier observations, suggest that both elevating HDL and lowering LDL cholesterol levels are effective in the primary prevention of CHD.

The Helsinki Heart Study is a coronary primary prevention trial in a group of middle aged men with lipid abnormalities. Its aim is to investigate the effects on the incidence of coronary heart disease of simultaneously lowering serum total and low density lipoprotein (LDL)-cholesterol and elevating high density lipoprotein (HDL)-cholesterol with gemfibrozil, over a period of 5 years. Participants were selected from a population of 23 531 men between 40 and 55 years of age. The mean serum total cholesterol among 18 966 screened subjects was 6.3 mmol l-1 (245 mg dl-1) and the mean HDL-cholesterol 1.3 mmol l-1 (50.3 mg dl-1). All subjects meeting the lipid acceptance criterion of non-HDL-cholesterol (i.e. total cholesterol minus HDL-cholesterol) greater than 5.2 mmol l-1 (200 mg dl-1) on two separate occasions two to three months apart, who were free from coronary heart disease or other major illness, were invited to participate. The total cholesterol level for the final 4081 study participants was 7.5 mmol l-1 (290 mg dl-1) and HDL-cholesterol was 1.23 mmol l-1 (47.6 mg dl-1). Mean systolic and diastolic blood pressures were 141.7 and 91.3 mmHg. About 15% of participants were hypertensive and 36% were smokers. A total of 2051 men were randomly allocated to receive gemfibrozil 600 mg twice daily and 2030 matching placebo capsules. A cholesterol-lowering diet was also prescribed for all participants. The randomized treatment groups were well balanced. Equal distribution of major risk factors was achieved in relevant sub-groups. This report describes the procedures involved in setting up the study, summarizes the baseline data obtained and reviews the success of the randomization procedure. Finally, it compares the design of this study with that of some other major preventive trials.