{
  "abstract": "Background Pharmacotherapy combinations have been shown to improve survival and reduce hospitalisations in adults with chronic heart failure with reduced ejection fraction (HFrEF); however, their cost-effectiveness when used as first-line treatment remains uncertain.Methods A lifetime cohort Markov model was developed from the perspective of the NHS in England to assess the cost-effectiveness of five first-line pharmacotherapy combinations: (i) angiotensin-converting enzyme inhibitor (ACEI) or angiotensin receptor blocker (ARB) and beta-blocker (BB) (NICE-recommended treatment at the time of analysis); (ii) ACEI/ARB, BB and mineralocorticoid receptor antagonists (MRA); (iii) angiotensin receptor-neprilysin inhibitor (ARNI), BB and MRA; (iv) ACEI/ARB, BB, MRA and sodium-glucose cotransporter-2 inhibitor (SGLT2i); and (v) ARNI, BB, MRA and SGLT2i. Baseline hospitalisation and mortality rates were informed by real-world data, while treatment effects (HRs) were derived from a review of randomised controlled trials.Results Among individuals able to tolerate an ACEI, the combination of ACEI, BB, MRA and SGLT2i (cost, £12 124; quality-adjusted life years (QALYs), 5.72) was found to be the most cost-effective first-line treatment option with an incremental cost-effectiveness ratio (ICER) of £7699.Among individuals unable to tolerate an ACEI, the combination of ARNI, BB, MRA and SGLT2i (cost, £18 950; QALYs, 6.04) was found to be the most cost-effective first-line treatment option with an ICER of £15 821. The next most cost-effective first-line treatment option was the combination of ARB, BB, MRA and SGLT2i (cost, £11 842; QALYs, 5.59). These findings were primarily driven by the greater relative QALY gain of ARNI compared with ARB.Conclusions This study demonstrates that a first-line quadruple pharmacotherapy combination is cost-effective compared with a stepwise approach for treating people with HFrEF, suggesting that wider adoption of early initiation of quadruple pharmacotherapy may improve health outcomes and optimise healthcare resource use.",
  "authors": [
    {
      "affiliations": [
        "Science, Evidence and Analytics Directorate, National Institute for Health and Care Excellence, London, UK"
      ],
      "name": "Alfredo Mariani"
    },
    {
      "affiliations": [
        "Science, Evidence and Analytics Directorate, National Institute for Health and Care Excellence, London, UK"
      ],
      "name": "Kirsty Luckham"
    },
    {
      "affiliations": [
        "Centre for Guidelines, National Institute for Health and Care Excellence, London, UK"
      ],
      "name": "Lisa Miles"
    },
    {
      "affiliations": [
        "Centre for Guidelines, National Institute for Health and Care Excellence, London, UK"
      ],
      "name": "Eleanor Samarasekera"
    },
    {
      "affiliations": [
        "Centre for Guidelines, National Institute for Health and Care Excellence, London, UK"
      ],
      "name": "Sharon Swain"
    },
    {
      "affiliations": [
        "Department of Non-communicable Disease Epidemiology, London School of Hygiene & Tropical Medicine, London, UK"
      ],
      "name": "Emily Herrett"
    },
    {
      "affiliations": [
        "Department of Non-communicable Disease Epidemiology, London School of Hygiene & Tropical Medicine, London, UK"
      ],
      "name": "Giulia Seghezzo"
    },
    {
      "affiliations": [
        "Department of Non-communicable Disease Epidemiology, London School of Hygiene & Tropical Medicine, London, UK"
      ],
      "name": "Laurie Tomlinson"
    },
    {
      "affiliations": [
        "Epsom and Saint Helier Hospital NHS Trust, London, UK"
      ],
      "name": "Hugh Gallagher"
    },
    {
      "affiliations": [
        "Liverpool Heart and Chest Hospital NHS Foundation Trust, Liverpool, UK"
      ],
      "name": "Joseph Mills"
    },
    {
      "affiliations": [
        "Sheffield Teaching Hospitals NHS Foundation Trust, Sheffield, UK"
      ],
      "name": "Abdallah Al-Mohammad"
    },
    {
      "affiliations": [
        "King’s College Hospital NHS Foundation Trust, London, UK"
      ],
      "name": "Susan Piper"
    },
    {
      "affiliations": [
        "Midlands Partnership NHS Foundation Trust, Stafford, UK"
      ],
      "name": "Duwarakan Satchithananda"
    },
    {
      "affiliations": [
        "Institute of Population Health, University of Liverpool, Liverpool, UK"
      ],
      "name": "Eduard Shantsila"
    },
    {
      "affiliations": [
        "Science, Evidence and Analytics Directorate, National Institute for Health and Care Excellence, London, UK"
      ],
      "name": "Syed Mohiuddin"
    },
    {
      "affiliations": [
        "Science, Evidence and Analytics Directorate, National Institute for Health and Care Excellence, London, UK"
      ],
      "name": "David Wonderling"
    }
  ],
  "title": "Model-based cost-effectiveness analysis of first-line pharmacotherapy combinations in adults with chronic heart failure and reduced ejection fraction",
  "uid": "410a1df9-7591-5a68-b357-762358436f8c"
}