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Primary prevention of ischaemic heart disease: WHO coordinated cooperative trial. A summary report
Insights
Lowering high serum cholesterol with clofibrate reduced ischaemic heart disease by 20%. However, this cholesterol-lowering drug significantly increased overall mortality, limiting its use.
Area of Science:
- Cardiology
- Preventive Medicine
- Pharmacology
Background:
- Elevated serum cholesterol is a known risk factor for ischaemic heart disease.
- The efficacy of lowering serum cholesterol to prevent clinically manifest ischaemic heart disease required further investigation.
Purpose of the Study:
- To determine if reducing elevated serum cholesterol levels could decrease the incidence of ischaemic heart disease.
- To assess the preventive value of lipid-lowering therapy in a controlled trial.
Main Methods:
- A double-blind trial involving middle-aged male volunteers with high serum cholesterol levels.
- Administration of clofibrate (a lipid-lowering substance) versus a placebo.
- Average observation period of 5.3 years.
Main Results:
- A 9% reduction in initial serum cholesterol levels was observed in the intervention group.
- A 20% reduction in the incidence of ischaemic heart disease occurred in the clofibrate group compared to the placebo group.
- Significant increases in total mortality and non-cardiovascular mortality were noted in the clofibrate group.
Conclusions:
- Lowering plasma lipid levels demonstrates preventive value against ischaemic heart disease.
- The observed increase in mortality associated with clofibrate use precludes its widespread application for cholesterol reduction.
- Further research is needed to understand the mechanisms behind the increased mortality in the clofibrate group.
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.