Statin Intensity and Selection

Statins (HMG-CoA reductase inhibitors) are the cornerstone of atherosclerotic cardiovascular disease (ASCVD) prevention. They competitively inhibit 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase, the rate-limiting enzyme in hepatic cholesterol biosynthesis. Reduced intracellular cholesterol upregulates hepatocyte LDL receptors, increasing clearance of LDL-C from the blood. Beyond LDL reduction, statins have pleiotropic effects: improved endothelial function (NO bioavailability), anti-inflammatory effects (reduced CRP), plaque stabilization (increased fibrous cap thickness, reduced lipid core), antithrombotic effects, and reduced oxidative stress. The 2018 ACC/AHA guidelines define statin intensity by expected LDL-C reduction: High-intensity (≥50% LDL reduction): atorvastatin 40-80 mg, rosuvastatin 20-40 mg. Moderate-intensity (30-49% LDL reduction): atorvastatin 10-20 mg, rosuvastatin 5-10 mg, simvastatin 20-40 mg, pravastatin 40-80 mg, lovastatin 40 mg, fluvastatin 80 mg, pitavastatin 1-4 mg. Low-intensity (<30% LDL reduction): simvastatin 10 mg, pravastatin 10-20 mg, lovastatin 20 mg. Four primary benefit groups for statin therapy: (1) clinical ASCVD, (2) LDL ≥190 mg/dL, (3) diabetes mellitus age 40-75, (4) estimated 10-year ASCVD risk ≥7.5% (age 40-75).