How do PCSK9 inhibitors like Repatha lower cholesterol, and how are they different from statins?

The liver removes LDL particles from blood using LDL receptors. PCSK9 helps send those receptors for destruction rather than recycling. Antibody drugs such as evolocumab, sold as Repatha, block PCSK9, leaving more receptors available to clear LDL. Statins work earlier in cholesterol metabolism by inhibiting cholesterol synthesis in the liver, which also encourages the liver to increase LDL uptake. Because the mechanisms differ, a PCSK9 treatment can add to the LDL reduction achieved with a statin.[1][2]

The key evidence is not just a better cholesterol panel. In FOURIER, adding evolocumab to statin therapy reduced cardiovascular events in people with established atherosclerotic disease. That does not make it automatically the best first treatment for every person with elevated cholesterol. Baseline cardiovascular risk, the remaining LDL reduction needed, tolerability, administration, cost and access all matter. PCSK9 treatment also does not neutralize other risks from smoking, hypertension or anabolic steroid exposure.[2][3]