PET Imaging of Inflammation and Lipid Lowering Study

Inclusion Criteria:

• Male or female participants >18 years old

• Able to give written, informed consent and to lie flat

• Have primary hypercholesterolaemia (non-familial or definite or possibleheterozygous familial hypercholesterolaemia (HeFH) based on clinical criteria) ormixed dyslipidaemia, and

• History of CVD (acute coronary syndrome, coronary or other revascularisationprocedures, coronary heart disease, ischaemic stroke, or peripheral arterialdisease) and elevated LDL cholesterol ≥2.6 despite maximum tolerated statins with orwithout other lipid lowering therapies (see NICE TA 733), and

• Lipid lowering therapy unchanged for at least 6 weeks prior to screening, and

• Pre-existing carotid atherosclerotic plaque ≥15mm by B-mode ultrasound

Exclusion Criteria:

• Women of childbearing potential not using adequate contraception

• Contra-indication to MRI scanning

• Statin-associated myositis or liver function abnormality

• Already taking inclisiran or colchicine

• Sensitivity and/or contraindication to inclisiran or colchicine. Contraindicationsto colchicine include severe hepatic or renal impairment, blood disorders, andpatients with renal or hepatic impairment who are taking a P-gp inhibitor or astrong CYP3A4 inhibitor

• Contrast allergy or contrast-nephropathy

• Chronic kidney disease (eGFR <30 mL/min/1.73 m2)

• Cardiovascular event within 6 months

• Any medical condition, in the opinion of the investigator, that prevents theparticipant from lying flat during scanning, or from participating in the study

• Uncontrolled chronic inflammatory disorder

• History of recent malignancy deemed relevant to the study by the investigator

• Treatment with medications that result in significant drug to drug interactions withthe study medications

• Current use of systemic corticosteroids or other immunosuppressive drugs

• Previous or planned carotid endarterectomy surgery or stenting on the index side