Metabolic modes of action of the statins in the hyperlipoproteinemias

Conflicting results have been published during the past few years regarding the physiologic modes of action of the hydroxymethylglutaryl-CoA (HMG-CoA) reductase inhibitors, generally referred to as statins, using standard dos es. Three mechanisms have been described: increased LDL catabolic rate, inc reased removal of LDL precursors resulting in decreased LDL production and decreased VLDL production. The physiologic effects of statins seem to depen d on the underlying pathology of the disorders under therapy. More recent d ata using either the more potent atorvastatin or larger doses of previously available statins (e.g. simvastatin 80-160 mg/day), suggest that both the potency of the statins and the underlying pathopysiology are important in d etermining the predominant physiologic responses of patients. To understand physiologic responses more completely, drug-dose-physiologic response curv es of apo B kinetics in various groups of patients are needed. Simultaneous studies of apo B, triglycerides and cholesterol metabolism are also needed and are currently feasible. (C) 1998 Elsevier Science Ireland Ltd. All rig hts reserved.