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 doses. Three mechanisms have been described: increased LDL catabolic rate, increased removal of LDL precursors resulting in decreased LDL production and decreased VLDL production. The physiologic effects of statins seem to depend on the underlying pathology of the disorders under therapy. More recent data 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 pathopHysiology are important in determining the predominant physiologic responses of patients. To understand physiologic responses more completely, drug-dose-physiologic response curves 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.