title: HEART UK statement on the management of homozygous familial hypercholesterolaemia in the United Kingdom.
abstract: This consensus statement addresses the current three main modalities of treatment of homozygous familial hypercholesterolaemia (HoFH): pharmacotherapy, lipoprotein (Lp) apheresis and liver transplantation. HoFH may cause very premature atheromatous arterial disease and death, despite treatment with Lp apheresis combined with statin, ezetimibe and bile acid sequestrants. Two new classes of drug, effective in lowering cholesterol in HoFH, are now licensed in the United Kingdom. Lomitapide is restricted to use in HoFH but, may cause fatty liver and is very expensive. PCSK9 inhibitors are quite effective in receptor defective HoFH, are safe and are less expensive. Lower treatment targets for lipid lowering in HoFH, in line with those for the general FH population, have been proposed to improve cardiovascular outcomes. HEART UK presents a strategy combining Lp apheresis with pharmacological treatment to achieve these targets in the United Kingdom (UK). Improved provision of Lp apheresis by use of existing infrastructure for extracorporeal treatments such as renal dialysis is promoted. The clinical management of adults and children with HoFH including advice on pregnancy and contraception are addressed. A premise of the HEART UK strategy is that the risk of early use of drug treatments beyond their licensed age restriction may be balanced against risks of liver transplantation or ineffective treatment in severely affected patients. This may be of interest beyond the UK.
authors.affiliation: Department of Clinical Biochemistry, Central Manchester University Hospitals, NHS Foundation Trust, Oxford Road, Manchester, M13 9WL, UK. Electronic address: michael.france@cmft.nhs.uk.
authors.forename: Michael
authors.initials: M
authors.lastname: France
authors.affiliation: HEART UK, 7 North Road, Maidenhead, Berkshire, SL6 1PE, UK.
authors.forename: Alan
authors.initials: A
authors.lastname: Rees
authors.affiliation: Lipid Unit, University Hospital, Llandough, Penlan Road, Penarth, Cardiff, CF62 2XX, UK.
authors.forename: Dev
authors.initials: D
authors.lastname: Datta
authors.affiliation: Clinical Lipidology, Imperial College London, Hammersmith Hospital, Du Cane Road, London, W12 ONN, UK.
authors.forename: Gilbert
authors.initials: G
authors.lastname: Thompson
authors.affiliation: Department of Clinical Biochemistry, Princess Royal Hospital, Apley Castle, Telford, Shropshire, TF1 6TF, UK.
authors.forename: Nigel
authors.initials: N
authors.lastname: Capps
authors.affiliation: Division of Medical Education, Clinical Director, Kent, Surrey and Sussex Clinical Research Network, Brighton and Sussex Medical School, University of Sussex, Brighton, East Sussex, BN1 9PX, UK.
authors.forename: Gordon
authors.initials: G
authors.lastname: Ferns
authors.affiliation: Lysosomal Disorders Unit, Institute of Immunity and Transplantation, 2nd Floor, Royal Free Hospital, Pond Street, London, NW3 2QG, UK.
authors.forename: Uma
authors.initials: U
authors.lastname: Ramaswami
authors.affiliation: Department of Cardiology, Imperial College Healthcare NHS Trust, Charing Cross Hospital, Fulham Palace Road, London, W6 8RF, UK.
authors.forename: Mary
authors.initials: M
authors.lastname: Seed
authors.affiliation: Department of Blood Sciences, Newcastle Upon Tyne Hospitals NHS Foundation Trust, Newcastle Upon Tyne, NE1 4LP, UK.
authors.forename: Dermot
authors.initials: D
authors.lastname: Neely
authors.affiliation: University Hospitals Birmingham, NHS Foundation Trust, Mindelsohn Way, Edgbaston, Birmingham, B15 2GW, UK.
authors.forename: Robert
authors.initials: R
authors.lastname: Cramb
authors.affiliation: William Harvey Research Institute, Queen Mary University, Charterhouse Square, London, EC1M 6BQ, UK.
authors.forename: Carol
authors.initials: C
authors.lastname: Shoulders
authors.affiliation: NHLI Imperial College, Royal Brompton & Harefield NHS Foundation Trust, Hill End Road, Harefield, Middlesex, UB9 6JH, UK.
authors.forename: Mahmoud
authors.initials: M
authors.lastname: Barbir
authors.affiliation: Royal Brompton and Harefield NHS Foundation Trust, Hill End Road, Harefield, Middlesex, UB9 6JH, UK.
authors.forename: Alison
authors.initials: A
authors.lastname: Pottle
authors.affiliation: Department of Medicine, Central Manchester University Hospitals, NHS Foundation Trust, Oxford Road, Manchester, M13 9WL, UK.
authors.forename: Ruth
authors.initials: R
authors.lastname: Eatough
authors.affiliation: Peterborough and Stamford Hospitals, NHS, Foundation Trust, Peterborough City Hospital, Bretton Gate, Peterborough, PE3 9GZ, UK.
authors.forename: Steven
authors.initials: S
authors.lastname: Martin
authors.affiliation: University Hospitals Bristol NHS Foundation Trust, Bristol, BS2 8HW, UK.
authors.forename: Graham
authors.initials: G
authors.lastname: Bayly
authors.affiliation: Aberdeen Royal Infirmary, Forester Hill, Aberdeen, AB25 2ZN, UK.
authors.forename: Bill
authors.initials: B
authors.lastname: Simpson
authors.affiliation: Swansea University (Prifysgol Abertawe), College of Medicine, Singleton Park, Swansea, SA2 8PP, UK.
authors.forename: Julian
authors.initials: J
authors.lastname: Halcox
authors.affiliation: HEART UK, 7 North Road, Maidenhead, Berkshire, SL6 1PE, UK.
authors.forename: Ray
authors.initials: R
authors.lastname: Edwards
authors.affiliation: Drummond Consultants Ltd, 3A Bowmans Close, Burnham, Buckinghamshire, SL1 8LH, UK.
authors.forename: Linda
authors.initials: L
authors.lastname: Main
authors.affiliation: HEART UK, 7 North Road, Maidenhead, Berkshire, SL6 1PE, UK.
authors.forename: Jules
authors.initials: J
authors.lastname: Payne
authors.affiliation: Department of Medicine and Cardiovascular Trials Unit, Central Manchester University Hospitals NHS Foundation Trust, Manchester, M139WL, UK; Cardiovascular Research Group, University of Manchester, Manchester, M139WL, UK.
authors.forename: Handrean
authors.initials: H
authors.lastname: Soran
authors.affiliation: Department of Medicine and Cardiovascular Trials Unit, Central Manchester University Hospitals NHS Foundation Trust, Manchester, M139WL, UK; Cardiovascular Research Group, University of Manchester, Manchester, M139WL, UK.
mesh_terms: D000911:Antibodies, Monoclonal / Q000009:adverse effects / Q000627:therapeutic use*; D061067:Antibodies, Monoclonal, Humanized; D000924:Anticholesteremic Agents / Q000009:adverse effects / Q000627:therapeutic use*; D001562:Benzimidazoles / Q000009:adverse effects / Q000627:therapeutic use*; D015415:Biomarkers / Q000097:blood; D001781:Blood Component Removal / Q000009:adverse effects / Q000379:methods*; D002318:Cardiovascular Diseases / Q000235:genetics / Q000517:prevention & control*; D002784:Cholesterol / Q000097:blood*; D003131:Combined Modality Therapy; D032921:Consensus; D020022:Genetic Predisposition to Disease; D006720:Homozygote; D006801:Humans; D006938:Hyperlipoproteinemia Type II / Q000097:blood / Q000175:diagnosis / Q000235:genetics / Q000628:therapy*; D009154:Mutation; D000091362:PCSK9 Inhibitors; D010641:Phenotype; D000071449:Proprotein Convertase 9 / Q000378:metabolism; D018570:Risk Assessment; D012307:Risk Factors; D016896:Treatment Outcome; D006113:United Kingdom
chemical_list: D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D000924:Anticholesteremic Agents; C473731:BMS201038; D001562:Benzimidazoles; D015415:Biomarkers; D000091362:PCSK9 Inhibitors; D002784:Cholesterol; C472125:PCSK9 protein, human; D000071449:Proprotein Convertase 9; C577155:evolocumab
keywords: Consensus; HEART UK; Homozygous familial hypercholesterolaemia; Lipoprotein apheresis; Lomitapide; evolocumab, proprotein convertase subtilisin kexin type 9