Quantitative coronary angiography to measure progression and regression of coronary atherosclerosis. Value, limitations, and implications for clinical trials.

T here have been five primary prevention trials of which the purpose was to determine whether reducing hypercholesterolemia would also decrease the incidence of coronary heart disease (CHD).1-5 Two were dietary studies, and three were pharmacological studies. Although there were inconsistencies in the findings among the trials, largely due to differences in design and method of intervention, each demonstrated significant reduc- tion in the incidence of CHD, particularly CHD morbidity, although none showed a convincing reduc- tion in total mortality. However, there is evidence to suggest that a synergistic effect occurs when interven- tions are combined, especially when one intervention is aimed at reducing hypercholesterolemia. For in- stance, the Oslo Heart Study showed an impressive reduction in CHD morbidity and mortality in previ- ously healthy men with the combined interventions of reducing cigarette smoking and lowering serum cho- lesterol levels by diet.6 Very recently, three trials showed, using repeated coronary angiography, that cholesterol lowering was associated with less progression of coronary artery disease and that the frequency of regression of lesions was increased.7-9 The establishment and successful conduct of new primary prevention trials of the effectiveness of lowering hypercholesterol- emia are very expensive and complex. Therefore, one of the most important questions now facing the medical and scientific community is whether it is possible to show that significant regression of cor- onary atherosclerotic lesions can be achieved by new and more powerful interventions that reduce From the Thorax Center (P.