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)
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:
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.