Optimizing lipid lowering in patients at risk.

The efficacy of statins in lowering low-density lipoprotein cholesterol (LDL-C) and reducing coronary heart disease risk is well established; however, recent evidence suggests that more aggressive lipid management, even beyond achievement of currently recommended LDL-C goals, may provide additional clinical benefits. A novel approach to the aggressive lowering of LDL-C is the combination of statins with agents that affect different aspects of cholesterol metabolism. Because absorption of cholesterol is an important contributor to cholesterol balance, the simultaneous inhibition of cholesterol absorption and cholesterol synthesis is an attractive approach to achieving greater LDL-C reductions. In clinical trials, the combination of the cholesterol absorption inhibitor ezetimibe with a statin resulted in greater improvements in lipids than statin monotherapy and allowed a greater percentage of patients to achieve treatment goals. In addition, this combination may offer benefits through reduction of phytosterols, chylomicron remnants, and C-reactive protein. Several ongoing trials are evaluating whether the benefit of simultaneously blocking cholesterol synthesis and intestinal cholesterol absorption translates into better clinical outcomes.