Which hyperlipidemic drug class works primarily by inhibiting HMG-CoA reductase?

Explanation

## Mechanism of Statins **Key Point:** Statins are competitive inhibitors of HMG-CoA reductase, the rate-limiting enzyme in cholesterol synthesis. ### Enzyme Target HMG-CoA reductase catalyzes the conversion of HMG-CoA to mevalonate, an early and crucial step in the cholesterol biosynthetic pathway. By inhibiting this enzyme, statins reduce intracellular cholesterol production. ### Downstream Effects 1. Decreased intracellular cholesterol levels 2. Upregulation of LDL receptors on hepatocyte surface 3. Increased clearance of LDL-cholesterol from blood 4. Net reduction in plasma LDL-C by 20–55% depending on statin potency ### Statin Classes by Potency | Statin | LDL-C Reduction | Typical Use | |--------|-----------------|-------------| | Atorvastatin | 30–55% | High-intensity | | Rosuvastatin | 35–55% | High-intensity | | Simvastatin | 25–35% | Moderate-intensity | | Pravastatin | 20–30% | Moderate-intensity | **High-Yield:** Statins are the most frequently prescribed hypolipidemics and are first-line for LDL-C reduction in both primary and secondary prevention of cardiovascular disease. **Clinical Pearl:** The cholesterol-lowering effect plateaus at about 30% inhibition of HMG-CoA reductase; further dose increases yield diminishing returns due to feedback compensation.