Table 7.

Assumptions used in the base-case scenario and scenario analyses

Feature	Scenario	Description
Cost-effectiveness threshold	£20,000 per QALY	NICE’s lower threshold
	£15,000 per QALY	Opportunity cost estimate used by the Department of Health and Social Care
	£30,000 per QALY	NICE’s upper threshold
Relative risk reduction	Event-specific relative reduction*	Used a different event-specific treatment effect for each outcome
	Single major cardiovascular events (MACE) relative reduction	Used MACE treatment effect for all CVD outcomes
Effect of LDL-C reduction on mortality	LDL-C reduction affects all-cause mortality*	Corresponding relative risk from CTT was applied to all-cause mortality
	LDL-C reduction affects CVD mortality only	Corresponding relative risk from CTT was applied to CVD mortality only
PCSK9 inhibitors	Inclisiran only*	Nobody escalated to PCSK9 inhibitors. People above the threshold who were taking ezetimibe received inclisiran
	PCSK9 inhibitors only	Nobody escalated to inclisiran. People above the threshold after taking ezetimibe received a PCSK9 inhibitor
	PCSK9 inhibitors at 3.5 mmol/L	People escalated to PCSK9 inhibitors if their LDL-C was above 3.5 mmol/L
Population	People on any statin*	Analysis on people on any statin
	People on atorvastatin 80mg	Used the age/sex/LDL-C distribution for the subgroup of people on atorvastatin 80 mg
	People on any statin and people who are statin intolerant	The base-case population ran through the model then the statin intolerant population ran through the model using an alternative treatment sequence. Both populations were treated to the same threshold and weighted average results were calculated
Angina	Include unstable angina*	Included unstable angina admissions
	Exclude unstable angina	Excluded angina from the model
TIA	Include TIA*	Included TIAs (costs only)
	Exclude TIA	Excluded TIA costs from the analysis
Quality of life weights	Health Survey for England 2017*	Applied the quality-of-life multipliers calculated from the HSE 2017
	Old version of statins model	Applied the quality-of-life multipliers used in the 2014 version of the NICE guideline (NG181)
	Inclisiran TA	Applied the quality-of-life multipliers used in the inclisiran TA
Adherence to ezetimibe	100% adherence*	Assumed a 100% adherence to ezetimibe
	80% adherence	Assumed an 80% adherence to ezetimibe (that is for 20% of patients with no cost of ezetimibe and no benefit either)
	50% adherence	Assumed a 50% adherence to ezetimibe (that is for 50% of patients with no cost of ezetimibe and no benefit either)
Adherence to injectable therapies	100% adherence*	Assumed a 100% adherence to injectable therapies
	80% adherence	Assumed an 80% adherence to injectable therapies (that is for 20% of patients with no cost and no benefit either)
	50% adherence	Assumed a 50% adherence to injectable therapies (that is for 50% of patients with no cost of ezetimibe and no benefit either)
Inclisiran price	Invoice price*	Used the invoice price of inclisiran that the NHS is currently charged for
	Volume discounted price	Used volume discounted price that is applicable once specific patient volumes are achieved
Escalation to inclisiran	One GP attendance*	Assumed that one GP attendance is sufficient to be prescribed inclisiran
	Two GP attendances and one nurse attendance	Added an extra GP attendance and a nurse-led attendance
Ezetimibe prescription fee	No prescription fee*	The cost of ezetimibe does not include the prescription fee paid to the pharmacist
	Including prescription fee	The cost of ezetimibe includes the prescription fee paid to the pharmacist
Cholesterol changes over time	Gradual constant lifetime increase adjusted for gender*	LDL-C changes over time using a gender-specific rate
	LDL-C regresses to the mean over 3 years	LDL-C change for three cycles using a gender, age and baseline cholesterol-adjusted model

*Base-case assumption