NICE guidance - Inclisiran for treating primary hypercholesterolaemia or mixed dyslipidaemia

NICE state (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
  • schaemic 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

Note that there have been concerns raised concerning the NICE technology appraisal for inclisiran (2):

• the Orion-9, Orion-10 and Orion-11 trials that the appraisal was based on had primary outcomes based on the change from baseline in participants' serum concentrations of LDL cholesterol - however LDL cholesterol is a surrogate outcome for cardiovascular disease, and doubts remain over whether improvements in surrogate endpoints are an accurate reflection of patient benefit
  • secondary outcomes included an exploratory cardiovascular endpoint -a composite of death, cardiac arrest, non-fatal myocardial infarction, and stroke - however the overall number of events was too low to draw conclusions
• the study authors concluded that "NICE should reconsider its decision until patient relevant outcomes are available, and these, and all cost data, should be released for independent analysis"

Reference:

• NICE (October 6th 2021). Inclisiran for treating primary hypercholesterolaemia or mixed dyslipidaemia.
• Byrne P et al. NICE guidance on inclisiran should be reconsidered. BMJ 2021; 375 doi: https://doi.org/10.1136/bmj.n2462