The future of lipid-lowering therapy: the big picture.

Several lipid-lowering intervention studies published in 2002 shed light on the current status and the future of cardiovascular risk reduction by drug therapy. The Heart Protection Study has demonstrated that simvastatin reduces heart attack, stroke and revascularisation risk by about one-third irrespective of total cholesterol, LDL cholesterol, patient's age or sex, or the nature of pre-existing cardiovascular disease. Coronary heart disease death and myocardial infarction risk reduction in elderly patients by pravastatin in the PROSPER study was similar to the benefit of statins in middle-aged populations in other studies. The ALLHAT-LLT study has failed to demonstrate a benefit of pravastatin on all-cause mortality, CHD death or nonfatal myocardial infarction, illustrating that too modest cholesterol lowering does not result in clinical benefit under all circumstances. The cholesterol absorption inhibitor ezetimibe has demonstrated significant LDL and total cholesterol lowering, and induced an additional 21% LDL cholesterol lowering when added to ongoing statin therapy. The cholesteryl ester transfer protein inhibitor JJT-705 produced a dose-dependent increase in HDL cholesterol concentrations of up to 34% and improved the total cholesterol/HDL cholesterol ratio in healthy individuals while having very mild side effects. Cholesterol absorption inhibitors and HDL cholesterol enhancers may become useful tools to achieve further improvements in cardiovascular risk reduction in the future.