Inclisiran for FH — EECC MCQ

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ModerateCardiac PharmacologyInclisiran for FHEECC

A 50-year-old woman with heterozygous familial hypercholesterolaemia on maximally tolerated rosuvastatin 40 mg and ezetimibe 10 mg has an LDL-C of 3.5 mmol/L (target <1.4 mmol/L for very high risk). She cannot tolerate PCSK9 monoclonal antibodies due to injection site reactions. What emerging option may be considered?

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Correct answer: D — Inclisiran — a small interfering RNA (siRNA) that inhibits hepatic PCSK9 production, administered subcutaneously every 6 months, providing sustained LDL-C reduction of approximately 50%

Inclisiran is a first-in-class small interfering RNA (siRNA) that targets PCSK9 mRNA in hepatocytes, reducing intracellular PCSK9 synthesis (unlike PCSK9 monoclonal antibodies which bind circulating PCSK9). This results in upregulation of LDL receptors and sustained LDL-C reduction of approximately 50% with only twice-yearly subcutaneous injections (after initial dosing at 0 and 3 months). The ORION trials demonstrated sustained efficacy and safety. The ESC/EAS Dyslipidaemia Guidelines include inclisiran as an option for patients not achieving LDL-C targets despite maximally tolerated statin + ezetimibe ± PCSK9 mAb. It may be particularly suitable for patients with adherence challenges (given 6-monthly dosing) or intolerance to PCSK9 mAbs.

Reference: ESC/EAS (2019/2025): Dyslipidaemia Guidelines; ORION Trials