Statins lower LDL primarily through which mechanism?

• A. Inhibit intestinal cholesterol absorption in the gut
• B. Competitive, reversible inhibition of HMG-CoA reductase
• C. Activation of PPAR-alpha
• D. Upregulation of PCSK9 expression

Answer: (B)

Statins lower LDL primarily by inhibiting the enzyme HMG-CoA reductase in the liver. This competitive, reversible inhibition reduces hepatic cholesterol synthesis, which lowers intracellular cholesterol. In response, hepatocytes upregulate LDL receptors, increasing clearance of LDL cholesterol from the blood and thus lowering LDL-C. This mechanism is distinct from agents that block intestinal cholesterol absorption (ezetimibe) or activate PPAR-alpha (fibrates). While statins can modestly increase PCSK9 levels, that is not the main way they reduce LDL; the key effect is HMG-CoA reductase inhibition leading to more LDL receptor–mediated clearance.