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How does cholesterol burden change the case for investing in familial hypercholesterolaemia? A cost-effectiveness analysis

      Highlights

      • The benefits of diagnosis and treatment of people with familial hypercholesterolaemia are large.
      • Considering cholesterol burden in cost-effectiveness modelling shows larger benefits from diagnosis and treatment.
      • The magnitude of benefits also depends on prognostic factors, in particular age and low-density lipoprotein cholesterol.

      Abstract

      Background and aims

      This study aimed to ascertain how the long-term benefits and costs of diagnosis and treatment of familial hypercholesterolaemia (FH) vary by prognostic factors and ‘cholesterol burden’, which is the effect of long-term exposure to low-density lipoprotein cholesterol (LDL-C) on cardiovascular disease (CVD) risk.

      Methods

      A new cost-effectiveness model was developed from the perspective of the UK National Health Service (NHS), informed by routine data from individuals with FH. The primary outcome was net health gain (i.e., health benefits net of the losses due to costs), expressed in quality-adjusted life years (QALYs) at the £15,000/QALY threshold. Prognostic factors included pre-treatment LDL-C, age, gender, and CVD history.

      Results

      If cholesterol burden is considered, diagnosis resulted in positive net health gain (i.e., it is cost-effective) in all individuals with pre-treatment LDL-C ≥ 4 mmol/L, and in those with pre-treatment LDL-C ≥ 2 mmol/L aged ≥50 years or who have CVD history. If cholesterol burden is not considered, diagnosis resulted in lower net health gain, but still positive in children aged 10 years with pre-treatment LDL-C ≥ 6 mmol/L and adults aged 30 years with pre-treatment LDL-C ≥ 4 mmol/L.

      Conclusions

      Diagnosis and treatment of most people with FH results in large net health gains, particularly in those with higher pre-treatment LDL-C. Economic evaluations of FH interventions should consider the sensitivity of the study conclusions to cholesterol burden, particularly where interventions target younger patients, and explicitly consider prognostic factors such as pre-treatment LDL-C, age, and CVD history.

      Graphical abstract

      Keywords

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      References

        • Mach F.
        • Baigent C.
        • Catapano A.L.
        • Koskinas K.C.
        • Casula M.
        • Badimon L.
        • Chapman M.J.
        • De Backer G.G.
        • Delgado V.
        • Ference B.A.
        • Graham I.M.
        • Halliday A.
        • Landmesser U.
        • Mihaylova B.
        • Pedersen T.R.
        • Riccardi G.
        • Richter D.J.
        • Sabatine M.S.
        • Taskinen M.R.
        • Tokgozoglu L.
        • Wiklund O.
        • Mueller C.
        • Drexel H.
        • Aboyans V.
        • Corsini A.
        • Doehner W.
        • Farnier M.
        • Gigante B.
        • Kayikcioglu M.
        • Krstacic G.
        • Lambrinou E.
        • Lewis B.S.
        • Masip J.
        • Moulin P.
        • Petersen S.
        • Petronio A.S.
        • Piepoli M.F.
        • Pinto X.
        • Raber L.
        • Ray K.K.
        • Reiner Z.
        • Riesen W.F.
        • Roffi M.
        • Schmid J.P.
        • Shlyakhto E.
        • Simpson I.A.
        • Stroes E.
        • Sudano I.
        • Tselepis A.D.
        • Viigimaa M.
        • Vindis C.
        • Vonbank A.
        • Vrablik M.
        • Vrsalovic M.
        • Gomez J.L.Z.
        • Collet J.P.
        • Windecker S.
        • Dean V.
        • Fitzsimons D.
        • Gale C.P.
        • Grobbee D.E.
        • Halvorsen S.
        • Hindricks G.
        • Iung B.
        • Jüni P.
        • Katus H.A.
        • Leclercq C.
        • Lettino M.
        • Merkely B.
        • Sousa-Uva M.
        • Touyz R.M.
        • Nibouche D.
        • Zelveian P.H.
        • Siostrzonek P.
        • Najafov R.
        • Van De Borne P.
        • Pojskic B.
        • Postadzhiyan A.
        • Kypris L.
        • Spinar J.
        • Larsen M.L.
        • Eldin H.S.
        • Strandberg T.E.
        • Ferrières J.
        • Agladze R.
        • Laufs U.
        • Rallidis L.
        • Bajnok L.
        • Gudjonsson T.
        • Maher V.
        • Henkin Y.
        • Gulizia M.M.
        • Mussagaliyeva A.
        • Bajraktari G.
        • Kerimkulova A.
        • Latkovskis G.
        • Hamoui O.
        • Slapikas R.
        • Visser L.
        • Dingli P.
        • Ivanov V.
        • Boskovic A.
        • Nazzi M.
        • Visseren F.
        • Mitevska I.
        • Retterstøl K.
        • Jankowski P.
        • Fontes-Carvalho R.
        • Gaita D.
        • Ezhov M.
        • Foscoli M.
        • Giga V.
        • Pella D.
        • Fras Z.
        • De Isla L.P.
        • Hagström E.
        • Lehmann R.
        • Abid L.
        • Ozdogan O.
        • Mitchenko O.
        • Patel R.S.
        ESC/EAS Guidelines for the management of dyslipidaemias: lipid modification to reduce cardiovascular risk.
        Eur. Heart J. 2019; 41: 111-188https://doi.org/10.1093/eurheartj/ehz455
        • National Institute for Health and Care Excellence (NICE), NICE CG71
        Familial Hypercholesterolaemia: Identification and Management.
        2008 (Last updated in 2019)., London, Manchester
        • Grundy S.M.
        • Stone N.J.
        • Bailey A.L.
        • Beam C.
        • Birtcher K.K.
        • Blumenthal R.S.
        • Braun L.T.
        • De Ferranti S.
        • Faiella-Tommasino J.
        • Forman D.E.
        • Goldberg R.
        • Heidenreich P.A.
        • Hlatky M.A.
        • Jones D.W.
        • Lloyd-Jones D.
        • Lopez-Pajares N.
        • Ndumele C.E.
        • Orringer C.E.
        • Peralta C.A.
        • Saseen J.J.
        • Smith S.C.
        • Sperling L.
        • Virani S.S.
        • Yeboah J.
        Guideline on the management of blood cholesterol: a report of the American college of cardiology/American heart association task force on clinical practice guidelines.
        Circulation. 2018; 139 (AHA/ACC/AACVPR/AAPA/ABC/ACPM/ADA/AGS/APhA/ASPC/NLA/PCNA): E1082-E1143https://doi.org/10.1161/CIR.0000000000000625
        • Nherera L.
        • Marks D.
        • Minhas R.
        • Thorogood M.
        • Humphries S.E.
        Probabilistic cost-effectiveness analysis of cascade screening for familial hypercholesterolaemia using alternative diagnostic and identification strategies.
        Heart. 2011; 97: 1175-1181https://doi.org/10.1136/hrt.2010.213975
        • Nherera L.
        • Calvert N.W.
        • DeMott K.
        • Humphries S.E.
        • Neil H.A.W.
        • Minhas R.
        • Thorogood M.
        Cost-effectiveness analysis of the use of a high-intensity statin compared to a low-intensity statin in the management of patients with familial hypercholesterolaemia.
        Curr. Med. Res. Opin. 2010; 26: 529-536https://doi.org/10.1185/03007990903494934
        • Crosland P.
        • Maconachie R.
        • Buckner S.
        • McGuire H.
        • Humphries S.E.
        • Qureshi N.
        Cost-utility analysis of searching electronic health records and cascade testing to identify and diagnose familial hypercholesterolaemia in England and Wales.
        Atherosclerosis. 2018; https://doi.org/10.1016/j.atherosclerosis.2018.05.021
        • Ademi Z.
        • Norman R.
        • Pang J.
        • Liew D.
        • Zoungas S.
        • Sijbrands E.
        • Ference B.
        • Wiegman A.
        • Watts G.F.
        Health economic evaluation of screening and treating children with familial hypercholesterolemia early in life: many happy returns on investment?.
        Atherosclerosis. 2020; https://doi.org/10.1016/j.atherosclerosis.2020.05.007
        • Ademi Z.
        • Watts G.F.
        • Juniper A.
        • Liew D.
        A systematic review of economic evaluations of the detection and treatment of familial hypercholesterolemia.
        Int. J. Cardiol. 2013; 167: 2391-2396https://doi.org/10.1016/j.ijcard.2013.01.280
        • Kerr M.
        • Pears R.
        • Miedzybrodzka Z.
        • Haralambos K.
        • Cather M.
        • Watson M.
        • Humphries S.E.
        Cost effectiveness of cascade testing for familial hypercholesterolaemia, based on data from familial hypercholesterolaemia services in the UK.
        Eur. Heart J. 2017; 38: 1832-1839https://doi.org/10.1093/eurheartj/ehx111
        • Vuorio A.
        • Docherty K.F.
        • Humphries S.E.
        • Kuoppala J.
        • Kovanen P.T.
        Statin treatment of children with familial hypercholesterolemia - trying to balance incomplete evidence of long-term safety and clinical accountability: are we approaching a consensus?.
        Atherosclerosis. 2013; 226: 315-320https://doi.org/10.1016/j.atherosclerosis.2012.10.032
        • Ference B.A.
        • Ginsberg H.N.
        • Graham I.
        • Ray K.K.
        • Packard C.J.
        • Bruckert E.
        • Hegele R.A.
        • Krauss R.M.
        • Raal F.J.
        • Schunkert H.
        • Watt G.F.
        • Borén J.
        • Fazio S.
        • Horton J.D.
        • Masana L.
        • Nicholls S.J.
        • Nordestgaard B.G.
        • van de Sluis B.
        • Taskinen M.R.
        • Tokgözoǧlu L.
        • Landmesser U.
        • Laufs U.
        • Wiklund O.
        • Stock J.K.
        • Chapman M.J.
        • Catapano A.L.
        Low-density lipoproteins cause atherosclerotic cardiovascular disease. 1. Evidence from genetic, epidemiologic, and clinical studies. A consensus statement from the European Atherosclerosis Society Consensus Panel.
        Eur. Heart J. 2017; 38: 2459-2472https://doi.org/10.1093/eurheartj/ehx144
        • National Institute of Health and Care Excellence (NICE)
        Guide to the Methods of Technology Appraisal.
        2013 (London, Manchester)
        • Stinnett A.A.
        • Mullahy J.
        Net health benefits: a new framework for the analysis of uncertainty in cost-effectiveness analysis.
        Med. Decis. Making. 1998; 18https://doi.org/10.1177/0272989x98018002s09
        • Department of Health & Social Care
        Association of British Pharmaceutical Industry, the 2019 Voluntary Scheme for Branded Medicines Pricing and Access.
        2018
        • Claxton K.
        • Martin S.
        • Soares M.
        • Rice N.
        • Spackman E.
        • Hinde S.
        • Devlin N.
        • Smith P.C.
        • Sculpher M.
        Methods for the estimation of the national Institute for health and care excellence cost-effectiveness threshold.
        Health Technol. Assess. 2015; 19: 1-503https://doi.org/10.3310/HTA19140
        • National Clinical Guideline Centre
        NICE CG181 Lipid Modification.
        2014 (London)
        • Cholesterol Treatment Trialists’ (CTT) Collaboration
        Efficacy and safety of statin therapy in older people: a meta-analysis of individual participant data from 28 randomised controlled trials.
        Lancet. 2019; 393: 407-415https://doi.org/10.1016/S0140-6736(18)31942-1
      1. N. Latimer, NICE DSU technical support document 14: survival analysis for economic evaluations alongside clinical trials - extrapolation with patient-level data, Sheffield (2011) 1-52.

        • Perak A.M.
        • Ning H.
        • de Ferranti S.D.
        • Gooding H.C.
        • Wilkins J.T.
        • Lloyd-Jones D.M.
        Long-term risk of atherosclerotic cardiovascular disease in US adults with the familial hypercholesterolemia phenotype.
        Circulation. 2016; 134: 9-19https://doi.org/10.1161/CIRCULATIONAHA.116.022335
        • Lewsey J.D.
        • Lawson K.D.
        • Ford I.
        • Fox K.A.A.
        • Ritchie L.D.
        • Tunstall-Pedoe H.
        • Watt G.C.M.
        • Woodward M.
        • Kent S.
        • Neilson M.
        • Briggs A.H.
        A cardiovascular disease policy model that predicts life expectancy taking into account socioeconomic deprivation.
        Heart. 2015; 101: 201-208https://doi.org/10.1136/heartjnl-2014-305637
        • National Institute of Health and Care Excellence (NICE)
        Familial Hypercholesterolaemia: Identification and Management.
        NICE guideline CG71, 2017
        • Ramaswami U.
        • Humphries S.E.
        • Priestley-Barnham L.
        • Green P.
        • Wald D.S.
        • Capps N.
        • Anderson M.
        • Dale P.
        • Morris A.A.
        Current management of children and young people with heterozygous familial hypercholesterolaemia - HEART UK statement of care.
        Atherosclerosis. 2019; 290: 1-8https://doi.org/10.1016/j.atherosclerosis.2019.09.005
        • Walker S.
        • Asaria M.
        • Manca A.
        • Palmer S.
        • Gale C.P.
        • Shah A.D.
        • Abrams K.R.
        • Crowther M.
        • Timmis A.
        • Hemingway H.
        • Sculpher M.
        Long-term healthcare use and costs in patients with stable coronary artery disease: a population-based cohort using linked health records (CALIBER).
        European Heart Journal - Quality of Care and Clinical Outcomes. 2016; 2: 125-140https://doi.org/10.1093/ehjqcco/qcw003
        • Ara R.
        • Brazier J.E.
        Populating an economic model with health state utility values: moving toward better practice.
        Value Health. 2010; 13: 509-518https://doi.org/10.1111/j.1524-4733.2010.00700.x
        • Pears R.
        • Griffin M.
        • Watson M.
        • Wheeler R.
        • Hilder D.
        • Meeson B.
        • Bacon S.
        • Byrne C.D.
        The reduced cost of providing a nationally recognised service for familial hypercholesterolaemia.
        Open Heart. 2014; 1https://doi.org/10.1136/openhrt-2013-000015
        • NHS England and NHS Improvement
        National Schedule of NHS Costs 2019.
        2020
        • Curtis L.A.
        • Burns A.
        Unit Costs of Health and Social Care 2019.
        University of Kent, 2019https://doi.org/10.22024/UniKent/01.02.79286
        • Briggs A.H.
        • Claxton Karl
        • Sculpher M.J.
        Decision Modelling for Health Economic Evaluation.
        2006: 237