Advertisement

The cost-effectiveness of omega-3 polyunsaturated fatty acids – The Australian healthcare perspective

  • Lan Gao
    Correspondence
    Corresponding author at: Deakin Health Economics, Institute for Health Transformation, Faculty of Health, Deakin University, 221 Burwood Hwy, Burwood, Melbourne, Australia.
    Affiliations
    Deakin Health Economics, Institute for Health Transformation, Deakin University, Geelong, Victoria, Australia

    Global Obesity Centre, Institute for Health Transformation, Deakin University, Geelong, Victoria, Australia

    School of Biomedical Sciences and Pharmacy, The University of Newcastle, Callaghan, NSW, Australia
    Search for articles by this author
  • Marj Moodie
    Affiliations
    Deakin Health Economics, Institute for Health Transformation, Deakin University, Geelong, Victoria, Australia

    Global Obesity Centre, Institute for Health Transformation, Deakin University, Geelong, Victoria, Australia
    Search for articles by this author
  • Shu-Chuen Li
    Affiliations
    School of Biomedical Sciences and Pharmacy, The University of Newcastle, Callaghan, NSW, Australia
    Search for articles by this author

      Highlights

      • The efficacy of icosapent ethyl in secondary prevention of CVD has been demonstrated.
      • We conducted a modelled economic evaluation based on efficacy data from a clinical trial.
      • Clinical data were derived from the key clinical trial that followed up patients for 5 years.
      • Icosapent ethyl was not considered cost-effective given the high US acquisition cost.

      Abstract

      Objectives

      To examine the cost-effectiveness of a triglyceride lowering medication–icosapent ethyl added on to statin from Australian healthcare system perspective.

      Methods

      A Markov-model was developed using data from the pivotal trial of icosapent ethyl in a secondary prevention population. Probabilities of CVD events were derived and extrapolated from the published Kaplan-Meier curve using a valid algorithm. Management cost of CVD, health-related quality of life, and background non-CVD mortality were extracted from publicly available sources. Acquisition cost of icosapent ethyl from the United States was used in the current analysis. Australian patients with histories of CVD were modelled for a 25 year time horizon and costs and benefits were discounted. Sensitivity analyses (SA) were undertaken. Value of perfect information (VPI) was quantified.

      Results

      Treatment with icosapent ethyl was associated with both higher costs and benefits (i.e. quality-adjusted life year [QALY] and life year [LY]), resulting in an incremental cost-effectiveness ratio (ICER) of AUD59,036/QALY or AUD54,358/LY. Using the often quoted willingness-to-pay (WTP)/QALY of AUD50,000/QALY, icosapent ethyl was not considered cost-effective. SA showed that time horizon, drug cost, and discount rate were the key drivers of the ICER. Total monetary VPI for icosapent ethyl was over AUD15 million over 5 years.

      Conclusions

      Patients with established CVD in whom level of triglycerides is high would benefit from the treatment using icosapent ethyl, however, it is not a cost-effective from an Australian healthcare system perspective. The government may consider subsidising this medication given the clinical need but at a discounted acquisition cost.

      Keywords

      To read this article in full you will need to make a payment

      Purchase one-time access:

      Academic & Personal: 24 hour online accessCorporate R&D Professionals: 24 hour online access
      One-time access price info
      • For academic or personal research use, select 'Academic and Personal'
      • For corporate R&D use, select 'Corporate R&D Professionals'

      Subscribe:

      Subscribe to European Journal of Internal Medicine
      Already a print subscriber? Claim online access
      Already an online subscriber? Sign in
      Institutional Access: Sign in to ScienceDirect

      References

        • Mozaffarian
        Heart disease and stroke statistics-2015 update: A report from the American Heart Association (vol 131, pg e29, 2015).
        Circulation. 2016; 133: E417-E
        • Australian Bureau of Statistics
        3303.0 - Causes of death, Australia.
        (Available from:) (Last accessed 15 Novemeber 2018. 2018)
        • Australian Institute of Health and Welfare
        Admitted patient care 2015–16: Australian hospital statistics.
        (Available from)
        • Cannon C.P.
        • Braunwald E.
        • McCabe C.H.
        • Rader D.J.
        • Rouleau J.L.
        • Belder R.
        • et al.
        Intensive versus moderate lipid lowering with statins after acute coronary syndromes.
        N Engl J Med. 2004; 350: 1495-1504
        • Fruchart J.C.
        • Sacks F.
        • Hermans M.P.
        • Assmann G.
        • Brown W.V.
        • Ceska R.
        • et al.
        The residual risk reduction initiative: a call to action to reduce residual vascular risk in patients with dyslipidemia.
        Am J Cardiol. 2008; 102: 1K-34K
        • Ferrari R.
        • Aguiar C.
        • Alegria E.
        • Bonadonna R.C.
        • Cosentino F.
        • Elisaf M.
        • et al.
        Current practice in identifying and treating cardiovascular risk, with a focus on residual risk associated with atherogenic dyslipidaemia.
        Eur Heart J Suppl. 2016; 18: C2-C12
        • Nordestgaard B.G.
        Triglyceride-rich lipoproteins and atherosclerotic cardiovascular disease: new insights from epidemiology, genetics, and biology.
        Circ Res. 2016; 118: 547-563
        • Reiner Z.
        Hypertriglyceridaemia and risk of coronary artery disease.
        Nat Rev Cardiol. 2017; 14: 401-411
        • Gandotra P.
        • Miller M.
        The role of triglycerides in cardiovascular risk.
        Curr Cardiol Rep. 2008; 10: 505-511
      1. The EPA drug initiative. FDA puts patients at risk, now says lowering triglycerides will not protect from heart attack and stroke.
        (Available from)
        http://epadruginitiative.com/press/fda-puts-patients-at-risk
        Date: 2013
        Date accessed: January 10, 2019
        • Ballantyne C.M.
        • Bays H.E.
        • Kastelein J.J.
        • Stein E.
        • Isaacsohn J.L.
        • Braeckman R.A.
        • et al.
        Efficacy and safety of eicosapentaenoic acid ethyl ester (AMR101) therapy in statin-treated patients with persistent high triglycerides (from the ANCHOR study).
        Am J Cardiol. 2012; 110: 984-992
        • Catapano A.L.
        • Graham I.
        • De Backer G.
        • Wiklund O.
        • Chapman M.J.
        • Drexel H.
        • et al.
        ESC/EAS Guidelines for the management of dyslipidaemias: The Task Force for the Management of Dyslipidaemias of the European Society of Cardiology (ESC) and European Atherosclerosis Society (EAS) developed with the special contribution of the European Assocciation for Cardiovascular Prevention & Rehabilitation (EACPR).
        Atherosclerosis. 2016; 253 (2016): 281-344
        • Grundy S.M.
        • Stone N.J.
        • Bailey A.L.
        • Beam C.
        • Birtcher K.K.
        • Blumenthal R.S.
        • et al.
        AHA/ACC/AACVPR/AAPA/ABC/ACPM/ADA/AGS/APhA/ASPC/NLA/PCNA guideline on the management of blood cholesterol: executive summary: a report of the American College of Cardiology/American Heart Association task force on clinical practice guidelines.
        J Am Coll Cardiol. 2018; 2018
        • Chapman M.J.
        • Ginsberg H.N.
        • Amarenco P.
        • Andreotti F.
        • Boren J.
        • Catapano A.L.
        • et al.
        Triglyceride-rich lipoproteins and high-density lipoprotein cholesterol in patients at high risk of cardiovascular disease: evidence and guidance for management.
        Eur Heart J. 2011; 32: 1345-1361
        • Cicero A.F.G.
        • Fogacci F.
        • Borghi C.
        Questioning the associations of ω-3 fatty acid supplement use with cardiovascular disease RisksQuestioning the associations of ω-3 fatty acid supplement use with cardiovascular disease RisksLetters.
        JAMA Cardiol. 2018; 3: 780-781
        • Cicero A.F.G.
        • Morbini M.
        • Borghi C.
        Do we need ‘new’ omega-3 polyunsaturated fatty acids formulations?.
        Expert Opin Pharmacother. 2015; 16: 285-288
        • Fares H.
        • Lavie C.J.
        • DiNicolantonio J.J.
        • O'Keefe J.H.
        • Milani R.V.
        Icosapent ethyl for the treatment of severe hypertriglyceridemia.
        Ther Clin Risk Manag. 2014; 10: 485-492
        • Bhatt D.L.
        • Steg P.G.
        • Miller M.
        • Brinton E.A.
        • Jacobson T.A.
        • Ketchum S.B.
        • et al.
        Cardiovascular risk reduction with Icosapent ethyl for hypertriglyceridemia.
        N Engl J Med. 2019; 380: 11-22
        • Chan L.N.
        Cardiovascular risk reduction with Icosapent ethyl.
        N Engl J Med. 2019; 380: 1677-1678
        • Yokoyama M.
        • Origasa H.
        • Matsuzaki M.
        • Matsuzawa Y.
        • Saito Y.
        • Ishikawa Y.
        • et al.
        Effects of eicosapentaenoic acid on major coronary events in hypercholesterolaemic patients (JELIS): a randomised open-label, blinded endpoint analysis.
        Lancet. 2007; 369: 1090-1098
        • Peterson A.V.
        Expressing the Kaplan-Meier estimator as a function of empirical subsurvival functions.
        J Am Stat Assoc. 1977; 72: 854-858
        • Guyot P.
        • Ades A.E.
        • Ouwens M.J.
        • Welton N.J.
        Enhanced secondary analysis of survival data: reconstructing the data from published Kaplan-Meier survival curves.
        BMC Med Res Methodol. 2012; 12: 9
        • Jackson C.H.
        Flexsurv: a platform for parametric survival Modeling in R.
        J Stat Softw. 2016; 70: 1-33
        • Latimer N.R.
        Survival analysis for economic evaluations alongside clinical trials--extrapolation with patient-level data: inconsistencies, limitations, and a practical guide.
        Med Decis Mak. 2013; 33: 743-754
        • Royston P.
        • Parmar M.K.
        Flexible parametric proportional-hazards and proportional-odds models for censored survival data, with application to prognostic modelling and estimation of treatment effects.
        Stat Med. 2002; 21: 2175-2197
        • Williams C.
        • Lewsey J.D.
        • Mackay D.F.
        • Briggs A.H.
        Estimation of survival probabilities for use in cost-effectiveness analyses: a comparison of a multi-state modeling survival analysis approach with partitioned survival and Markov decision-analytic modeling.
        Med Decis Mak. 2017; 37: 427-439
        • Australian Bureau of Statistics
        3303.0 Causes of death, Australia.
        (Available from:)
        • Independent Hospital Pricing Authority
        National efficient price determination 2018–19.
        (Available from) (Last accessed 11 Jan 2019. 2017)
        • Khera R.
        • Valero-Elizondo J.
        • Saxena A.
        • Virani S.S.
        • Krumholz H.M.
        • Nasir K.
        National population and cost implications of treatment with Icosapentyl ethyl in the United States: An assessment based on the REDUCE-IT trial. bioRxiv.
        2018 (466649)
        • Cobiac L.J.
        • Magnus A.
        • Barendregt J.J.
        • Carter R.
        • Vos T.
        Improving the cost-effectiveness of cardiovascular disease prevention in Australia: a modelling study.
        BMC Public Health. 2012; 12
        • Wang S.
        • Gum D.
        • Merlin T.
        Comparing the ICERs in medicine reimbursement submissions to NICE and PBAC—does the presence of an explicit threshold affect the ICER proposed?.
        Value Health. 2018; 21: 938-943
        • Australian Institute of Health and Welfare
        Cardiovascular disease webpages data tables.
        2018
        • Australian Bureau of Statistics
        4364.0.55.005 - Australian health survey: Biomedical results for chronic diseases, 2011–12.
        (Available from)
        • Claxton K.
        • Palmer S.
        • Longworth L.
        • Bojke L.
        • Griffin S.
        • McKenna C.
        • et al.
        Informing a decision framework for when NICE should recommend the use of health technologies only in the context of an appropriately designed programme of evidence development.
        Health Technol Assess. 2012; 16 (1-+)
        • Eckermann S.
        • Willan A.R.
        Expected value of information and decision making in HTA.
        Health Econ. 2007; 16: 195-209
        • Australian Bureau of Statistics
        Australian health survey: Biomedical results for chronic diseases, 2011-2012.
        Aug 2013 ([Cat. No. 4364.55.005])
        • De Smedt D.
        • Kotseva K.
        • De Bacquer D.
        • Wood D.
        • De Backer G.
        • Dallongeville J.
        • et al.
        Cost-effectiveness of optimizing prevention in patients with coronary heart disease: the EUROASPIRE III health economics project.
        Eur Heart J. 2012; 33: 2865-2872
        • Wei C.Y.
        • Quek R.G.W.
        • Villa G.
        • Gandra S.R.
        • Forbes C.A.
        • Ryder S.
        • et al.
        A systematic review of cardiovascular outcomes-based cost-effectiveness analyses of lipid-lowering therapies.
        Pharmacoeconomics. 2017; 35: 297-318
        • Tsevat J.
        • Kuntz K.M.
        • Orav E.J.
        • Weinstein M.C.
        • Sacks F.M.
        • Goldman L.
        Cost-effectiveness of pravastatin therapy for survivors of myocardial infarction with average cholesterol levels.
        Am Heart J. 2001; 141: 727-734
        • Ballantyne C.M.
        • Bays H.E.
        • Philip S.
        • Doyle Jr., R.T.
        • Braeckman R.A.
        • Stirtan W.G.
        • et al.
        Icosapent ethyl (eicosapentaenoic acid ethyl ester): effects on remnant-like particle cholesterol from the MARINE and ANCHOR studies.
        Atherosclerosis. 2016; 253: 81-87
        • Shearer G.C.
        • Savinova O.V.
        • Harris W.S.
        Fish oil - how does it reduce plasma triglycerides?.
        BBA-Mol Cell Biol L. 2012; 1821: 843-851
        • Kumar R.
        • Tonkin A.
        • Liew D.
        • Zomer E.
        The cost-effectiveness of PCSK9 inhibitors - the Australian healthcare perspective.
        Int J Cardiol. 2018; 267: 183-187
        • Griffin S.C.
        • Claxton K.P.
        • Palmer S.J.
        • Sculpher M.J.
        Dangerous omissions: the consequences of ignoring decision uncertainty.
        Health Econ. 2011; 20: 212-224
        • Walker S.
        • Sculpher M.
        • Claxton K.
        • Palmer S.
        Coverage with evidence development, only in research, risk sharing, or patient access scheme? A framework for coverage decisions.
        Value Health. 2012; 15: 570-579
        • Gorby H.E.
        • Brownawell A.M.
        • Falk M.C.
        Do specific dietary constituents and supplements affect mental energy? Review of the evidence.
        Nutr Rev. 2010; 68: 697-718
        • Galarraga B.
        • Ho M.
        • Youssef H.M.
        • Hill A.
        • McMahon H.
        • Hall C.
        • et al.
        Cod liver oil (n-3 fatty acids) as an non-steroidal anti-inflammatory drug sparing agent in rheumatoid arthritis.
        Rheumatology (Oxford). 2008; 47: 665-669
        • Cicero A.F.
        • Reggi A.
        • Parini A.
        • Borghi C.
        Application of polyunsaturated fatty acids in internal medicine: beyond the established cardiovascular effects.
        Arch Med Sci. 2012; 8: 784-793