Atorvastatin: a hydroxymethylglutaryl-coenzyme A reductase inhibitor

The pharmacology, pharmacokinetics, clinical efficacy, adverse effects, interactions, and formulary considerations of atorvastatin relative to other hydroxymethylglutaryl-coenzyme A (HMG-CoA) reductase inhibitors (statins) are discussed. Atorvastatin calcium, a synthetic stereoisomer of a pentasubstituted pyrrole, prevents the conversion of HMG-CoA by competitive and selective inhibition of HMG-CoA reductase. This limits cholesterol formation. Atorvastatin undergoes extensive first-pass metabolism; the first-pass effect is saturable at higher doses. Time to maximum plasma concentration ranges from one to four hours. The plasma elimination half-life is considerably longer than for other statins. Like other statins, atorvastatin reduces low-density-lipoprotein cholesterol (LDL-C) and total cholesterol in patients with hypercholesterolemia. However, the reductions achieved with atorvastatin exceed those for other statins. Atorvastatin recipients are more likely to achieve LDL-C goals and to do so more quickly. Atorvastatin also moderately reduces triglyceride levels in patients with hypertriglyceridemia and may play a role in the management of familial hypercholesterolemia. Adequate lipid control with atorvastatin monotherapy may preclude the need for combination drug therapy in some patients. The adverse effects of atorvastatin include mild gastrointestinal disturbances, increased liver enzyme levels, and myalgia. Drug interactions involving atorvastatin can be expected to parallel those of other statins metabolized via CYP3A4. Atorvastatin has become a popular addition to hospital formularies, even though formal pharmacoeconomic analyses are lacking. Atorvastatin effectively reduces blood lipids and may offer some advantages over other statins, but more studies are needed to clarify its optimal role in pharmacotherapy.