Primary prevention of ischaemic heart disease: WHO coordinated cooperative trial. A summary report

Abstract

Elevated serum cholesterol concentrations are known to be predictive of ischaemic heart disease. It remained to be proven, however, whether reduction of clinically manifest ischaemic heart disease could be achieved by the lowering of elevated serum-cholesterol levels. In order to create a clear and simple unifactorial study design, a lipid-lowering substance (clofibrate) was administered to this effect in a double-blind trial to middle-aged male volunteers whose serum cholesterol levels were within the upper third of the distribution in their respective populations (Budapest, Edinburgh, Prague). After an average of 5.3 years of observation, and with a reduction of some 9% of the initial serum cholesterol levels, the incidence of ischaemic heart disease was reduced by 20% in the intervention group as compared with the placebo group, thus demonstrating the preventive value of lowering this plasma lipid. There was, however, a significant increase in total mortality and in non-cardiovascular mortality in the clofibrate group, precluding the community-wide use of this drug for reduction of serum cholesterol. The explanation of this is not clear, but possible mechanisms are discussed.