Current and future aims of lipid-lowering therapy: changing paradigms and lessons from the Heart Protection Study on standards of efficacy and safety.

Lipid-lowering guidelines continue to evolve toward the use of (1) global risk assessment, (2) lipid measures other than or in addition to low-density lipoprotein (LDL) cholesterol in assessment of risk and treatment benefit, and (3) recommendations for more aggressive lipid lowering. Findings in the Heart Protection Study (HPS) indicate that high-risk patients benefit from statin therapy initiated at a dose that provides aggressive lowering of LDL cholesterol. Statin treatment in this trial provided consistent benefits in reducing major vascular events among a wide variety of high-risk patients, including those beginning treatment with LDL cholesterol levels <100 mg/dL. The HPS findings therefore suggest that the optimal LDL cholesterol level is well below current target levels. In addition, they provide reassurance that aggressive statin therapy is safe. Frequently, current targets for LDL cholesterol are not achieved in clinical practice, particularly among those patients who have coronary artery disease or are at high risk of disease. More intensive lipid lowering than that currently practiced is necessary to achieve current goals and to provide the aggressive reduction of LDL cholesterol shown to improve outcomes in clinical trials. New statins, such as rosuvastatin, offer the prospect of improved lipid-lowering therapy.