RATIONALE FOR TREATMENT

Based on substantial evidence, the 1984 NIH Consensus Development Conference concluded that the treatment of total and low-density lipoprotein (LDL) cholesterol elevations with diet and, when necessary, with drugs, can reduce the risk of coronary artery disease (CAD). Accordingly, in 1988 the National Cholesterol Education Program (NCEP) published guidelines for defining moderate-, borderline-high-, and high-risk categories for CAD. Many clinical trials have supported the benefits of antihyperlipidemic therapy. Evidence from the Coronary Primary Prevention Trial gave rise to the "2:1 ratio," i.e., that a l% reduction in total cholesterol level is associated with a 2% decrease in CAD events. The Helsinki Heart Study results indicated that additional benefit may be obtained by raising high-density lipoprotein (HDL)-cholesterol levels. Dramatic reductions in LDL and total cholesterol were achieved by the Program on the Surgical Control of the Hyperlipidemias, which also achieved a 35% reduction in CAD events and a two-thirds reduction in both coronary bypass operations and angioplasties. Long-term benefits of cholesterol lowering in terms of cardiovascular and all-cause mortality have been shown in the Coronary Drug project and the Multiple Risk Factor Intervention Trial. Two major studies that have documented angiographic changes as a result of cholesterol lowering are the Cholesterol-Lowering Atherosclerosis Study (CLAS) and the Familial Atherosclerosis Treatment Study (FATS). In both CLAS and FATS, there was a decrease in the development of new lesions and a lowering of the rate of progression of existing lesions. In FATS, there was also evidence that aggressive antihyperlipidemic therapy will decrease existing lesions in some CAD patients.