This site is intended for healthcare professionals

Go to /sign-in page

You can view 5 more pages before signing in

Go to /pro/cpd-dashboard page

This page is worth 0.05 CPD credits. CPD dashboard

Go to /account/subscription-details page

This page is worth 0.05 CPD credits. Upgrade to Pro

Inclisiran

Authoring team

Inclisiran is recommended as a treatment option in treating primary hypercholesterolaemia (heterozygous familial and non-familial) or mixed dyslipidaemia as an adjunct to diet in adults.

Familial hypercholesterolaemia is characterised by an elevated level of low-density lipoprotein (LDL) cholesterol and an increased risk of premature atherosclerotic cardiovascular disease. (1)

Lowering LDL-C levels is therefore a key part of all cardiovascular disease prevention guidelines, which recommend matching the intensity of LDL-C lowering with the absolute risk of the patient. Unfortunately, issues such as statin intolerance or difficulties with long-term adherence to statin therapy and a subsequent inability to achieve desired LDL-C levels with statins alone results in a continuing raised cardiovascular disease risk. (2)

Pharmacologic management of familial hypercholesterolaemia includes the use of high-intensity statins, ezetimibe, and monoclonal antibodies directed against circulating PCSK9.

PCSK9 is a circulating protein primarily produced and secreted by hepatocytes that regulates LDL receptor half-life in the liver. It functions primarily by altering LDL receptor recycling via binding the receptor and facilitating its transport into lysosomes for degradation (3)

Inclisiran (Leqvio 248mg) is a small interfering RNA that inhibits PCSK9, thereby upregulating the number of LDL-receptors on the hepatocytes. It is administered by subcutaneous injection twice a year, after an initial baseline and 3 month dose.

It is recommended only if: (4)

  • there is a history of any of the following cardiovascular events:
    • acute coronary syndrome (such as myocardial infarction or unstable angina needing hospitalisation)
    • coronary or other arterial revascularisation procedures
    • coronary heart disease
    • ischaemic stroke or
    • peripheral arterial disease, and
  • low-density lipoprotein cholesterol (LDL-C) concentrations are persistently 2.6 mmol/l or more, despite maximum tolerated lipid-lowering therapy, that is
    • maximum tolerated statins with or without other lipid-lowering therapies or,
    • other lipid-lowering therapies when statins are not tolerated or are contraindicated

Note - there have been concerns raised concerning the NICE technology appraisal for inclisiran (see related page) (5)

Results are also being awaited from the Orion-4 trial: a double-blind randomised placebo-controlled trial assessing the effects of inclisiran on clinical outcomes among people with atherosclerotic cardiovascular disease. This study aims to find out whether inclisiran, given every 6 months for about 5 years, safely reduces the risk of heart attacks, strokes or the need for urgent coronary angioplasty or bypass grafts, in people who already have known vascular disease (6).

Reference:

  1. Amor-Salamanca A, Castillo S, Gonzalez-Vioque E, et al. Genetically confirmed familial hypercholesterolemia in patients with acute coronary syndrome. J Am Coll Cardiol 2017;70:1732-1740.
  2. Ference BA, Ginsberg HN, Graham I, et al. Low-density lipoproteins cause atherosclerotic cardiovascular disease. 1. Evidence from genetic, epidemiologic, and clinical studies: a consensus statement from the European Atherosclerosis Society Consensus Panel. Eur Heart J 2017;38:2459-2472.
  3. Warden BA, Duell PB. Inclisiran: a novel agent for lowering apolipoprotein B–containing lipoproteins. J Cardiovasc Pharmacol. 2021;78:e157–e174.
  4. NICE. Inclisiran for treating primary hypercholesterolaemia or mixed dyslipidaemia. Technology appraisal guidance TA733. Published October 2021
  5. Byrne P et al. NICE guidance on inclisiran should be reconsidered. BMJ 2021; 375
  6. NHS Health Research Authority. ORION-4. HPS-4/TIMI 65/ORION-4: A double-blind randomized placebo-controlled trial assessing the effects of inclisiran on clinical outcomes among people with atherosclerotic cardiovascular disease. 2025. (Online.)

Create an account to add page annotations

Annotations allow you to add information to this page that would be handy to have on hand during a consultation. E.g. a website or number. This information will always show when you visit this page.

The content herein is provided for informational purposes and does not replace the need to apply professional clinical judgement when diagnosing or treating any medical condition. A licensed medical practitioner should be consulted for diagnosis and treatment of any and all medical conditions.

Connect

Copyright 2025 Oxbridge Solutions Limited, a subsidiary of OmniaMed Communications Limited. All rights reserved. Any distribution or duplication of the information contained herein is strictly prohibited. Oxbridge Solutions receives funding from advertising but maintains editorial independence.