Non‑statin LDL‑lowering medications

Non‑statin agents can lower LDL cholesterol substantially and, for several of them, reduce cardiovascular events, but statins remain first‑line because they have the most robust, long‑term outcome data and are inexpensive. The main non‑statin classes are: 1. Ezetimibe oral tablet that blocks intestinal cholesterol absorption; adds about a 15‑25% LDL reduction and has proven event‑reduction benefit when added to a statin or used alone in statin‑intolerant patients. 2. PCSK9 inhibitors (alirocumab, evolocumab) subcutaneous injections every 24 weeks; produce large LDL drops (≈50‑60%) and have strong outcome data; used when LDL goals are not met with statins or when statin intolerance exists; cost is higher. 3. Inclisiran small interfering RNA (siRNA) therapy given on day 0, at 3 months, then every 6 months; yields LDL reductions similar to PCSK9 antibodies; outcomes trial results are pending. 4. Bempedoic acid oral pro‑drug activated in the liver; useful in statin‑intolerant patients; modest LDL lowering (≈15‑20%) and recent trials show cardiovascular benefit. 5. Icosapent ethyl omega‑3 fatty‑acid formulation that lowers triglycerides and addresses residual risk but does not significantly lower LDL. In practice, clinicians tailor therapy to achieve a low LDL/ApoB target, balancing efficacy, side‑effect profile, cost, and patient preference. Non‑statin options are effective alternatives, especially for those who cannot tolerate statins or need additional LDL lowering beyond what statins provide.