Current and emerging strategies for treating dyslipidemia and macrovascular disease

Statins, inhibitors of hydroxymethylglutaryl CoA (HMG-CoA) reductase, have been in clinical use for over 20 years. The widespread use of these agents has left doubt of the efficacy of cholesterol-lowering therapy to prevent cardiovascular disease. In spite of the widespread use of these agents and the successful lowering of circulating cholesterol together with reduction of cardiovascular-related deaths, there is consensus that further improvements in therapy are needed. Cardiovascular disease remains a major cause of premature death and continues to exert an extensive drain on the health-care costs. This chapter outlines some of the emerging strategies for discovering and developing novel treatments of dyslipidemia and macrovascular disease. Mechanisms considered include alternate ways to lower total cholesterol through inhibition of synthesis, limitation of absorption, or recycling. Other approaches include the modification of circulating forms of cholesterol and changes in gene expression at the key sites of storage, utilization, and pathology. The next successful strategy will likely be one that works well in concert with existing statins.