atorvastatin

Atorvastatin inhibits HMG-CoA reductase, the rate-limiting enzyme in the mevalonate pathway of cholesterol biosynthesis, primarily in the liver. Reduced intracellular cholesterol synthesis leads to upregulation of hepatic LDL receptors, increasing clearance of LDL particles from circulation. This results in significant reductions in LDL-C (up to 50-60% at high doses), modest reductions in triglycerides, and modest increases in HDL. Statins also have pleiotropic effects including anti-inflammatory properties and plaque stabilization, contributing to cardiovascular risk reduction beyond lipid lowering alone. Atorvastatin is a high-intensity statin (along with rosuvastatin) at appropriate doses (40-80mg), used per ACC/AHA guidelines for four major statin benefit groups: clinical atherosclerotic cardiovascular disease (ASCVD), LDL ≥190 mg/dL, diabetes age 40-75 with LDL 70-189, and estimated 10-year ASCVD risk ≥7.5% with risk factors. Key adverse effects include hepatotoxicity (monitor LFTs), myopathy/myalgia and rare rhabdomyolysis (risk increased with fibrates, especially gemfibrozil, and CYP3A4 inhibitors since atorvastatin is metabolized by CYP3A4), and new-onset diabetes mellitus. It is contraindicated in pregnancy (Category X) due to teratogenic effects on fetal cholesterol synthesis necessary for development. Statins are typically taken at bedtime historically (though atorvastatin has long half-life allowing any-time dosing) since cholesterol synthesis peaks at night. Drug interactions are important: grapefruit juice inhibits CYP3A4 and can increase statin levels; combination with fibrates or niacin increases myopathy risk. Monitoring includes baseline and periodic LFTs, and CK levels if muscle symptoms occur. Statins are contraindicated in active liver disease.