Safety of high-dose atorvastatin therapy.
This article reviews the safety of statins, with emphasis on high-dose atorvastatin (80 mg), the agent with the most efficacy data for clinical outcomes. Although elevated levels of hepatic enzymes were of concern when statins were first introduced, a review of data from large clinical trials shows that elevations in hepatic enzymes are rare and do not lead to clinically significant liver disease. Despite the withdrawal of cerivastatin because of fatal rhabdomyolysis, the risk of this complication with other statins is extremely low. Mild and often transient myalgia is more commonly reported. The safety of high-dose atorvastatin has been evaluated in >11,000 patients, and rates of clinically significant myopathy and elevated hepatic enzymes were extremely low. Simvastatin at doses up to 40 mg is also associated with low rates of elevated hepatic enzymes and myopathy. However, the 80-mg dose of simvastatin carries a risk of myopathy (muscle symptoms and creatine kinase levels >10,000 U/L) of approximately 1 in 250. The clinical benefits of preventing vascular events, myocardial infarction, stroke, and need for revascularization outweigh the low rates of adverse events associated with high-dose statin therapy in high- and intermediate-risk patients.
Waters
David D
DD
Division of Cardiology, San Francisco General Hospital and the School of Medicine, University of California, San Francisco, California 94110, USA. dwaters@medsfgh.ucsf.edu
D000069059:Atorvastatin; D004334:Drug Administration Schedule; D006538:Heptanoic Acids / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D006801:Humans; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D009203:Myocardial Infarction / Q000517:prevention & control*; D011758:Pyrroles / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D019821:Simvastatin / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*
D006538:Heptanoic Acids; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D011758:Pyrroles; D000069059:Atorvastatin; D019821:Simvastatin