The relative role of low-density lipoprotein cholesterol and high-density lipoprotein cholesterol in coronary artery disease: evidence from large-scale statin and fibrate trials

Statin therapy has been remarkably successful in reducing coronary events and improving survival. Reduction in low-density lipoprotein cholesterol (LDL-C) is the paramount mechanism for the benefit of statins. Although the relation between reduction of risk of coronary artery disease and pretreatment lipid levels has not been fully resolved, a feature of statin therapy emerging from previous large-scale trials is the diminished benefit when the baseline level of LDL-C is low (eg, <125 mg/dL). Increases in levels of high-density lipoprotein cholesterol (HDL-C) with statin therapy are associated with mild reductions in coronary events, indicating that HDL-C is an important element. However, the risk of low HDL-C is not altered by statin therapy, in marked contrast with LDL-C. Because most coronary events have not been prevented in the statin trials, nonstatin lipid therapy, including fibrates, may be necessary to further reduce the unacceptably high rate of coronary artery disease.