Clinical trials including an update on the Helsinki heart study

Abstract

The incidence of myocardial infarction (MI), sudden death and other clinical manifestations of coronary heart disease can be reduced by lowering the blood cholesterol level. This is now well established by multiple clinical trials using a variety of interventions including diet and lipid-lowering drugs. Dietary studies in Los Angeles and in Oslo, Norway, have induced a reduction in blood cholesterol of between 10 and 15% with correlated reductions in coronary disease of 20 to 50%. Both niacin and clofibrate in separate cohorts demonstrated a significant reduction in new MI during 5 years of treatment in the Coronary Drug Project. Similar reductions in new MI occurred in the World Health Organization Study with clofibrate. However, in this trial and different from all other trials, mortality in the drug-treatment group actually increased. This finding remains unexplained. In the more recent Lipid Research Clinics Coronary Primary Prevention Trial using the bile acidbinding resin cholestyramine, only a 9% reduction in total cholesterol resulted in a highly significant reduction in the major end points—MI and sudden death—as well as in other secondary end points, including the need for coronary artery bypass graft surgery, ischemic changes on exercise electrocardiography and new-onset angina. Recently, another primary prevention trial using gemfibrozil produced a similar reduction in total cholesterol but a much more significant increase in high-density lipoprotein cholesterol. The reduction in coronary heart disease was in excess of 34% and was strongly related to both low-density lipoprotein cholesterol reduction and high-density lipoprotein elevation. Combination drug studies have produced larger reductions in total cholesterol. In the Stockholm Heart Study, niacin and clofibrate produced a statistically significant reduction in total mortality in patients who had had recent Ml. Similarly, in men who had undergone coronary artery bypass graft surgery, the combination of niacin, colestipol and diet produced strong evidence of a reduced rate of progression of arteriosclerotic lesions as demonstrated by coronary angiography. This study, conducted at the University of Southern California, was the Cholesterol-Lowering Atherosclerosis Study. It also produced evidence of lesion regression in some patients. Although these studies have been carried out primarily in middle-aged men, the older segments of these populations have appeared to do as well with regard to disease prevention as the younger members of the cohorts. We can now treat patients with high blood cholesterol levels both before and after manifestation of coronary disease with significant assurance that beneficial effects will accrue. Additional studies with newer and more powerful lipid-lowering agents are needed, as are studies in women and the elderly.