The evolving role of statins in the management of atherosclerosis

Significant advances in the management of cardiovascular disease have been made possible by the development of 3-hydroxy-3-methylglutaryl coenzyme A ( HMG CoA) reductase inhibitors-"statins." Initial studies explored the impac t of statin therapy on coronary artery disease (CAD) progression and regres sion. Although the angiographic changes were small, associated clinical res ponses appeared significant. Subsequent large prospective placebo-controlle d clinical trials with statins demonstrated benefit in the secondary and pr imary prevention of CAD in subjects with elevated cholesterol levels. More recently, the efficacy of statins has been extended to the primary preventi on of CAD in subjects with average cholesterol levels. Recent studies also suggest that statins have benefits beyond the coronary vascular bed and are capable of reducing ischemic stroke risk by approximately one-third in pat ients with evidence of vascular disease. In addition to lowering low-densit y Lipoprotein (LDL) cholesterol, statin therapy appears to exhibit pleiotro pic effects on many components of atherosclerosis including plaque thrombog enicity, cellular migration, endothelial function and thrombotic tendency. Growing clinical and experimental evidence indicates that the beneficial ac tions of statins occur rapidly and yield potentially clinically important a ntiischemic effects as early as one month after commencement of therapy. Fu ture investigations are warranted to determine threshold LDL values in prim ary prevention studies, and to elucidate effects of statins other than LDL lowering. Finally, given the rapid and protean effects of statins on determ inants of platelet reactivity, coagulation, and endothelial function, furth er research may establish a role for statin therapy in acute coronary syndr omes. (C) 1999 by the American College of Cardiology.