## Management of Statin-Inadequate LDL Lowering **Key Point:** When LDL cholesterol remains above target despite adequate statin therapy (6+ weeks at therapeutic dose), the next step is to add a non-statin agent—ezetimibe is the first-line add-on before escalating to PCSK9 inhibitors or other agents. ### Stepwise Approach to Hypercholesterolaemia | Step | Action | LDL Reduction | Indication | |------|--------|---------------|------------| | 1 | Statin monotherapy (atorvastatin 40–80 mg) | 40–55% | First-line | | 2 | Add ezetimibe 10 mg | Additional 15–20% | Statin-inadequate response | | 3 | Increase statin to high-intensity (atorvastatin 80 mg) | Additional 5–10% | If ezetimibe insufficient | | 4 | Add PCSK9 inhibitor | Additional 50–60% | Very high-risk or familial hypercholesterolaemia | **High-Yield:** Ezetimibe works by inhibiting cholesterol absorption in the small intestine (NPC1L1 transporter) and is synergistic with statins. It has no hepatic or muscle toxicity and is safe to combine. **Clinical Pearl:** This patient has been on atorvastatin 40 mg for only 6 weeks at a submaximal dose. Before jumping to PCSK9 inhibitors (cost, frequency, indication), add ezetimibe and/or uptitrate the statin. ### Why Not the Other Options? **Switching statins (option B):** Rosuvastatin is more potent than atorvastatin, but switching without adding a complementary agent wastes the opportunity for synergy and delays goal achievement. **PCSK9 inhibitors (option D):** Reserved for very high-risk patients (established CAD, familial hypercholesterolaemia, or LDL >100 mg/dL despite maximal statin + ezetimibe). This patient has not yet exhausted dual therapy. **Mnemonic:** **STEP-UP** — Statin → Then Ezetimibe → PCSK9 inhibitor → Uptitrate statin in parallel → Proprotein convertase inhibitors for refractory cases.
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