Abstract
Atorvastatin is the fifth HMG-CoA reductase inhibitor approved for use in the U.S. The mechanism of action of atorvastatin appears to be similar to other agents in the class. Atorvastatin is metabolized by cytochrome P450 3A4 to several active metabolites. Approximately 70% of the lipid lowering effect of atorvastatin is attributed to its metabolites. Atorvastatin's efficacy is greater than that of other available HMG-CoA reductase inhibitors. At 10 mg/day, atorvastatin reduces LDL cholesterol by 39% and triglycerides by 19%. At the highest FDA approved dose of 80 mg/day, atorvastatin reduces LDL cholesterol by 60% and triglycerides by 37%. Atorvastatin 10 mg/day produces LDL cholesterol reductions that are similar to or greater than the LDL cholesterol reductions achieved with all doses up to 40 mg/day with the other HMG-CoA reductase inhibitors. Atorvastatin is associated with a very low incidence of dose-limiting side effects with a discontinuation rate of less than 2%. The most common side effects are constipation, flatulence, dyspepsia, and abdominal pain. In comparative trials against other HMG-CoA reductase inhibitors, no significant differences in the incidence of side effects were observed. As with other HMG-CoA reductase inhibitors, combined use of atorvastatin with erythromycin, cyclosporin, fibric acid derivatives, niacin, and azole antifungals increases the risk of myopathy. Atorvastatin represents a highly effective HMG-CoA reductase inhibitor that produces greater reductions in LDL cholesterol and triglycerides than other currently available agents in this class. Based on NCEP treatment guidelines in which predetermined LDL cholesterol levels are the goal of therapy, atorvastatin appears to fill a major void that exists with current therapy. For patients requiring a 40% or greater reduction in LDL cholesterol, atorvastatin is the only agent capable of such reductions. The major unresolved issue with atorvastatin is its unknown impact on cardiovascular morbidity and mortality.