Aggressive lipid-lowering therapy: a clinical imperative.

Abstract

Overwhelming evidence from epidemiological and clinical studies has demonstrated that low density lipoprotein cholesterol (LDL-C) is a key element in the development of atherosclerosis, and that reducing LDL-C levels results in a lower risk of coronary heart disease (CHD). As a result, greater emphasis is being placed on the need for effective cholesterol reduction in individuals at risk of CHD. Early lipid-lowering trials, using fibrates and bile acid sequestrants, achieved only modest reductions in plasma LDL-C, and had a disappointing impact on total mortality. Recent studies using more effective lipid-lowering agents--3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase inhibitors--demonstrated more substantial reductions in cholesterol and were associated with significant reductions in coronary, and all-cause, mortality. However, the extent of LDL-C reduction achieved often fell short of LDL-C treatment targets recommended in national and international guidelines. Analysis of data from a range of studies suggests that more aggressive lipid-lowering therapy results in a greater reduction in the risk of major coronary events. However, it is not only the final LDL-C level achieved that affects CHD risk, but also the degree of cholesterol lowering that has occurred, such that the lower the level of LDL-C achieved, the greater the benefit in terms of reduced CHD events. Patients that demonstrate the greatest changes in LDL-C levels seem to benefit most from lipid-lowering treatment.