BackgroundNumerous reports suggest that coronary artery disease can regress with lipoprotein manipulation. Many of these reports lack control groups and contain relatively small numbers.Methods and ResultsTen randomized controlled clinical trials using coronary arteriography to assess the effect of lipoprotein manipulation on the rate of progression and regression of atherosclerosis have been either published or reported as an abstract at a national meeting. These studies were critically reviewed for individual differences and combined clinically applicable lessons. These trials involved a total of 2095 subjects and have consistently reported reduction in the percentage of patients arteriographically defined as progressing (mean, 23.6%) and an increase in the percentage regressing (mean, 20.0%) compared with control groups. Com-pared with large clinical trials using clinical end points, lipoprotein change was greater, achieving on average a 28% reduction in low-density lipoprotein cholesterol, 11% reduction in triglycerides, and 1% increase in high-density lipoprotein cholesterol compared with control groups. Four investigations used a nonpharmacological approach, and seven used single and multiple drug therapy combined with diet. Despite the relatively brief treatment time of often 2 to 4 years, clinical events were fewer in the treatment groups; within some studies, this reached statistical significance. Side effects from the different therapies were tolerated by most patients, and severe adverse clinical events were few.ConclusionsThese trials present convincing evidence that aggressive lipoprotein manipulation can result in improved arteriographic measurements and fewer cardiovascular events in a relatively short period of time of 2 to 4 years. Extrapolation of this information to the larger population with known coronary artery disease suggests that directed lipoprotein manipulation can reduce clinical events in a cost-effective manner.