A 58-year-old man with heterozygous familial hypercholesterolaemia has been taking Atorvastatin 80 mg and Ezetimibe 10 mg for the past 6 months. His LDL remains above 3.5 mmol/L despite good adherence. What is the most appropriate next step?

• A. Inclisiran SC injection
• B. Ezetimibe 10 mg
• C. Fibrate therapy
• D. PCSK9 monoclonal antibody IV

Answer: (A)

When someone with heterozygous familial hypercholesterolaemia remains above target LDL despite maximally tolerated statin plus ezetimibe, you escalate by adding a therapy that targets the PCSK9 pathway. Inclisiran is a small interfering RNA that reduces hepatic production of PCSK9, which increases LDL receptor availability on liver cells and lowers LDL by about half when added to statin therapy. A key advantage is its dosing schedule: subcutaneous injections initially at day 0 and day 90, then every 6 months, offering a convenient, long-acting option that can aid adherence.

In contrast, PCSK9 monoclonal antibodies are also effective but are given more frequently (typically as injections every 2–4 weeks) and the option that states IV administration is not accurate, since these antibodies are administered subcutaneously. Repeating ezetimibe or using fibrates won’t provide the needed LDL lowering in familial hypercholesterolaemia. Therefore, the best next step is Inclisiran SC injection.