A double-blind intervention trial was started in 1965 to test the hypothesis that the incidence of ischaemic heart disease in middle-aged men can be reduced by lowering raised serum cholesterol levels. It was carried out in 3 European centres - Edinburgh, Budapest, and Prague. Serum cholesterol was to be lowered by the drug clofibrate (ethyl chlorophenoxyisobutyrate) which was considered to be free from serious side effects. Studies were carried out on 15 745 males, aged 30 to 59 at entry, for an average of 5.3 years, accumulating 83 534 years of experience. The treatment group, of about 5000, Group I, was a randomly chosen half of the men in the upper third of the serum cholesterol distribution in some 30 000 volunteers. The comparable control group, Group II, comprised the other 5000 men of the upper third of the cholesterol distribution, and these were given a placebo. A further control group, Group III, of 5000 men, was selected randomly from the lower third of the cholesterol distribution. These numbers were chosen in order to be 90 per cent certain of detecting a 30 per cent reduction in the incidence of ischaemic heart disease should this occur. Subjects with manifest heart or other major disease were excluded from the trial. No attempt was made to correct other 'risk factors' for IHD, but their presence was monitored and considered in the analysis. Investigators and participants in the trial were unaware of the groups to which individual men belonged. A mean reduction of approximately 9 per cent of the initial serum cholesterol levels was achieved in the treatment group (ranging from 7 to 11% in the 3 centres); this was less than the 15 per cent fall expected. In Edinburgh, during treatment, serum triglyceride concentrations in Group I resembled those naturally occurring in Group III. The incidence of IHD was lower by 20 per cent in the clofibrate group compared with the high cholesterol controls (P< 0.05); this fall was confined to non-fatal myocardial infarcts which were reduced by 25 per cent. The incidence of fatal heart attacks was similar in the 2 high cholesterol groups and there was no significant difference in the incidence of angina. Group III showed substantially lower rates of ischaemic heart disease. The reduction of myocardial infarction in the clofibrate-treated group was greatest in men with the highest levels, and greatest reduction in serum cholesterol. Men with a substantial reduction of cholesterol concentration, who smoked, and also had above average blood pressure levels showed the most benefit. The numbers of deaths, and crude mortality rates from all causes in the clofibrate-treated group significantly exceeded those in the high cholesterol control group (P < 0.05), though the age-standardised mortality rates did not differ significantly between the 3 groups. The numbers of deaths from 'other.
ASJC Scopus subject areas
- Cardiology and Cardiovascular Medicine