Does aggressive statin therapy offer improved cholesterol-independent benefits compared to conventional statin treatment?

There is currently intense research interest in the properties of HMG-CoA reductase inhibitors (statins) beyond their well-documented lipid-lowering action. Studies have consistently demonstrated that administration of statin therapy decreases levels of the inflammatory marker C-reactive protein (CRP), a marker associated with an increased risk of cardiovascular events. This effect appears to be independent of the extent of reduction in total or LDL-cholesterol. Statins also appear to improve endothelial dysfunction by increasing endothelium-dependent vasodilatation. There is also evidence that statins inhibit fibrin formation and thrombus development, an effect that which would be clinically beneficial following plaque fissure or rupture. Early preclinical and clinical evidence suggests that there are quantitative differences between statin regimens in terms of their cholesterol-independent properties. Trials comparing equipotent doses of different statins, based on lipid-lowering efficacy, have not reported any differences in cholesterol-independent properties. However, the current evidence base indicates that more aggressive statin regimens are associated with an enhanced anti-inflammatory effect. Intensive lipid-lowering using statin therapy generates a greater reduction in mortality than standard lipid management, and it is possible that enhanced cholesterol-independent effects may account for some of this excess benefit. (C) 2004 Elsevier Ireland Ltd. All rights reserved.