Icosapent Ethyl for Primary Versus Secondary Prevention of Major Adverse Cardiovascular Events in Hypertriglyceridemia: Value for Money Analysis

Published:January 11, 2021DOI:



      Icosapent ethyl (IPE) is approved for the prevention of major adverse cardiovascular events (MACE) in patients with hypertriglyceridemia. However, due to budget constraints, access to IPE will inevitably be limited to a fraction of eligible patients. To help maximize value for money spent, we estimated the number of preventable MACE when providing IPE for primary versus secondary prevention.


      The number of preventable MACE was estimated by dividing the available budget by the cost needed to treat (CNT) to prevent one MACE. CNT was calculated as the product of the number needed to treat (NNT) to prevent 1 MACE by therapy cost. NNT values were determined according to the Reduction of Cardiovascular Events with Icosapent Ethyl–Intervention Trial (REDUCE-IT) results. The budget limit was set as the United States’ threshold suggested by the Institute for Clinical and Economic Review. Sensitivity analysis was performed regarding the cost of IPE in the United States.


      The NNT to prevent 1 MACE over 4.9 years in the Reduction of Cardiovascular Events with Icosapent Ethyl–Intervention Trial primary prevention cohort was 59 (95% confidence interval [CI]: 24-∞) versus 14 (11-21) for secondary prevention. At an annual IPE cost of $2915, the CNT to prevent 1 MACE was $842,726 (95% CI: $342,804-∞) and $199,969 ($157,118-$299,953) accordingly. A total of $819 million worth of IPE can avoid 4762 MACE (95% CI: 0-11,707) versus 20,069 (13,379-25,541), when provided as primary versus secondary prevention therapy; P < .001. The number of avoided MACE is sensitive to IPE price.


      Prioritizing IPE therapy for patients with an established cardiovascular disease may provide significantly more value for money than primary prevention.


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        • Toth PP
        • Philip S
        • Hull M
        • Granowitz C
        Association of elevated triglycerides with increased cardiovascular risk and direct costs in statin-treated patients.
        Mayo Clin Proc. 2019; 94: 1670-1680
        • Bhatt DL
        • Steg PG
        • Miller M
        • et al.
        Cardiovascular risk reduction with icosapent ethyl for hypertriglyceridemia.
        N Engl J Med. 2019; 380: 11-22
      1. US Food and Drug Administration. FDA approves use of drug to reduce risk of cardiovascular events in certain adult patient groups. Available at: Accessed January 16, 2020.

        • Skulas-Ray AC
        • Wilson PWF
        • Harris WS
        • et al.
        Omega-3 fatty acids for the management of hypertriglyceridemia: a science advisory from the American Heart Association.
        Circulation. 2019; 140: e673-e691
      2. Standards of medical care in diabetes-2020; 10. Cardiovascular disease and risk management: diabetes care. 2020;43:S111-134.

        • Orringer CE
        • Jacobson TA
        • Maki KC
        National Lipid Association Scientific Statement on the use of icosapent ethyl in statin-treated patients with elevated triglycerides and high or very-high ASCVD risk.
        J Clin Lipidol. 2019; 13: 860-872
      3. Ollendorf D, McQueen R, Campbell J, et al. Final Evidence Report: Additive Therapies for Cardiovascular Disease: Effectiveness and Value. Available at: Accesed May 19, 2020.

        • Case BC
        • Bress A
        • Kolm P
        • et al.
        The economic burden of hypertriglyceridemia among US adults with diabetes or atherosclerotic cardiovascular disease on statin therapy.
        J Clin Lipidol. 2019; 13: e20-e22
      4. FDA Endocrinologic and Metabolic Drugs Advisory Subcommittee. Amarin Pharmaceuticals Ireland Limited Advisory Committee Briefing Document on Vascepa® (icosapent ethyl; AMR101). Available at: Accessed August 5, 2020.

        • Suissa D
        • Brassard P
        • Smiechowski B
        • Suissa S
        Number needed to treat is incorrect without proper time-related considerations.
        J Clin Epidemiol. 2012; 65: 42-46
        • Bender R
        • Kromp M
        • Kiefer C
        • Sturtz S
        Absolute risks rather than incidence rates should be used to estimate the number needed to treat from time-to-event data.
        J Clin Epidemiol. 2013; 66: 1038-1044
      5. Centers for Medicare & Medicaid Services. National average drug acquisition cost. Available at: Accessed August 5, 2020.

        • Levy J
        • Rosenberg M
        • Vanness D
        A transparent and consistent approach to assess US outpatient drug costs for use in cost-effectiveness analyses.
        Value Heal. 2018; 21: 677-684
        • Jia X
        • Akeroyd JM
        • Nasir K
        • et al.
        Eligibility and cost for icosapent ethyl based on the reduce-it trial: Insight from the veterans affairs healthcare system.
        Circulation. 2019; 139: 1341-1343
        • Pearson SD
        The ICER value framework: integrating cost effectiveness and affordability in the assessment of health care value.
        Value Heal. 2018; 21: 258-265
        • Chade DS
        • Obenshain SS
        • Ramo B
        • Eaton RP
        A feasible, simple, cost-saving program to end cardiovascular disease in the United States.
        Am J Med. 2019; 132: 1365-1367
        • Gao L
        • Moodie M
        • Li SC
        The cost-effectiveness of omega-3 polyunsaturated fatty acids – the Australian healthcare perspective.
        Eur J Intern Med. 2019; 67: 70-76
      6. Ademi Z, Ofori-Asenso R, Zomer E, Owen A, Liew D. The cost-effectiveness of icosapent ethyl in combination with statin therapy compared with statin alone for cardiovascular risk reduction [e-pub ahead of print]. Eur J Prev Cardiol. Accessed month day, year. doi: 10.1177/2047487319896648. Accesed May 19, 2020

        • Altman DG
        Confidence intervals for the number needed to treat.
        BMJ. 1998; 317: 1309-1312
        • Bhatt DL
        • Steg PG
        • Miller M
        • et al.
        Effects of icosapent ethyl on total ischemic events: from REDUCE-IT.
        J Am Coll Cardiol. 2019; 73: 2791-2802