1 Recommendations

1.1 Inclisiran is recommended as an option for treating primary hypercholesterolaemia (heterozygous familial and non-familial) or mixed dyslipidaemia as an adjunct to diet in adults. It is recommended only if:

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, and
the company provides inclisiran according to the commercial arrangement.

1.2 Inclisiran is recommended only in research for treating primary hypercholesterolaemia (heterozygous familial and non-familial) or mixed dyslipidaemia in adults who have no history of cardiovascular events. This research is in the form of a clinical trial currently in development.

1.3 These recommendations are not intended to affect treatment with inclisiran that was started in the NHS before this guidance was published. People having treatment outside these recommendations may continue without change to the funding arrangements in place for them before this guidance was published, until they and their NHS clinician consider it appropriate to stop.

Why the committee made these recommendations

Current treatment for primary hypercholesterolaemia (heterozygous familial and non-familial) or mixed dyslipidaemia includes statins for lowering LDL-C levels. Ezetimibe and either alirocumab or evolocumab may be added when a person's LDL-C levels are not lowered enough with the maximum tolerated dose of statins. Inclisiran would be used when statins or other lipid-lowering therapies do not control LDL-C well enough or when people cannot have statins.

Clinical trial evidence shows that inclisiran can lower LDL-C levels when statins or other lipid-lowering therapies have not reduced them enough. But, there is no data directly comparing inclisiran with ezetimibe, alirocumab or evolocumab. There is also no long-term evidence on whether inclisiran reduces cardiovascular events. This means the clinical evidence and the cost-effectiveness estimates are very uncertain.

But, despite the uncertainties, inclisiran is still considered cost effective in people who have previously had a cardiovascular event and have persistently high LDL-C levels (2.6 mmol/l or more) despite maximum lipid-lowering therapy. Therefore, inclisiran is recommended as an option in this population.

In people who have never had a cardiovascular event, the cost-effectiveness estimates were very uncertain and likely to be above what NICE considers an acceptable use of NHS resources. But, a clinical trial is planned that will look at inclisiran's effect on cardiovascular events in this population. So in this population, inclisiran is recommended only in research.