{
  "abstract": "Heart failure with reduced ejection fraction carries a poor prognosis. Although guideline-directed medical therapy reduces morbidity and mortality, its real-world utilization is low. Accordingly, we conducted an open-label randomized trial (POLY-HF) at two centers enrolling a predominantly underserved population to test whether a polypill strategy improves cardiac function in heart failure. Adults with heart failure and left ventricular ejection fraction ≤40% were randomized to a once-daily polypill containing metoprolol succinate (25/50/100/150 mg), spironolactone 12.5 mg and empagliflozin 10 mg, or rapid uptitration of individual guideline-directed medical therapy medications ('enhanced usual care'). Participants also continued treatment with a renin-angiotensin system inhibitor or sacubitril/valsartan as a separate pill. The primary endpoint was ejection fraction as assessed by cardiac magnetic resonance imaging at 6 months. Secondary endpoints included clinical outcomes and adherence. We randomized 212 patients (median age 54 years, 22% female, 54% Black). Follow-up magnetic resonance imaging data were available for 187 (88%) participants who were included in the modified intention-to-treat analysis. Polypill treatment was associated with greater improvement in ejection fraction compared to enhanced usual care (between-group difference, 3.3 percentage points, 95% confidence interval, 0.2-6.4; P = 0.039), meeting the primary outcome. Individuals randomized to the polypill also had a 60% lower rate of heart failure hospitalizations or emergency department visits (adjusted rate ratio, 0.40; 95% confidence interval, 0.18-0.88; P = 0.024). Adherence, assessed by blood concentrations of metoprolol and spironolactone, was higher with polypill treatment than with enhanced usual care (79% versus 54%, P = 0.001). The polypill was well tolerated, with fewer adverse events with polypill treatment as compared to enhanced usual care. A polypill for heart failure was associated with a significant improvement in cardiac function as compared with enhanced usual care. ClinicalTrials.gov registration: NCT04633005 .",
  "abstract_shown": true,
  "affiliations": [
    "Department of Internal Medicine, Division of Cardiology, UT Southwestern Medical Center, Dallas, TX, USA. ambarish.pandey@utsouthwestern.edu",
    "Baylor Scott and White Research Institute Dallas, Baylor Scott and White The Heart Hospital, Plano, TX, USA",
    "Department of Internal Medicine, Division of Cardiology, UT Southwestern Medical Center, Dallas, TX, USA",
    "Advanced Imaging Research Center, UT Southwestern Medical Center, Dallas, TX, USA",
    "Department of Cardiology, Texas Heart Institute, Houston, TX, USA",
    "Department of Medicine, Vanderbilt University Medical Center, Nashville, TN, USA",
    "Department of Pharmacy Practice and Pharmaceutical Science, Lipscomb University College of Pharmacy, Nashville, TN, USA",
    "Division of Cardiovascular Medicine, Vanderbilt University Medical Center, Nashville, TN, USA",
    "Vanderbilt Translational and Clinical Cardiovascular Research Center, Vanderbilt University Medical Center, Nashville, TN, USA",
    "Department of Pediatrics, Division of Pediatric Cardiology, University of Texas Southwestern Medical Center, Dallas, TX, USA",
    "Department of Radiology, Division of Pediatric Radiology, University of Texas Southwestern Medical Center, Dallas, TX, USA",
    "University of Michigan Medical School, Ann Arbor, MI, USA"
  ],
  "article_type": null,
  "arxiv": null,
  "author_total": 19,
  "authors": [
    {
      "affs": [
        0
      ],
      "name": "Ambarish Pandey",
      "orcid": "0000-0001-9651-3836"
    },
    {
      "affs": [
        1,
        2
      ],
      "name": "Neil Keshvani",
      "orcid": "0000-0001-6890-8670"
    },
    {
      "affs": [
        2
      ],
      "name": "Syed K. Rizvi"
    },
    {
      "affs": [
        3
      ],
      "name": "Fatemeh Khashami",
      "orcid": "0009-0006-1151-8026"
    },
    {
      "affs": [
        2
      ],
      "name": "Katarina Yaros"
    },
    {
      "affs": [
        2
      ],
      "name": "Muhammad Usman",
      "orcid": "0000-0001-9747-8892"
    },
    {
      "affs": [
        4
      ],
      "name": "Matthew W. Segar",
      "orcid": "0000-0001-6100-0897"
    },
    {
      "affs": [
        2
      ],
      "name": "Anand K. Jain",
      "orcid": "0009-0006-3432-2667"
    },
    {
      "affs": [
        2
      ],
      "name": "Juan David Coellar"
    },
    {
      "affs": [
        2
      ],
      "name": "Myriam Bustillo-Rubio"
    },
    {
      "affs": [
        5,
        6
      ],
      "name": "Zachary L. Cox",
      "orcid": "0000-0002-4919-0146"
    },
    {
      "affs": [
        2
      ],
      "name": "Jennifer T. Thibodeau",
      "orcid": "0000-0001-9131-685X"
    },
    {
      "affs": [
        2
      ],
      "name": "Chul Ahn"
    },
    {
      "affs": [
        7,
        8
      ],
      "name": "Deepak K. Gupta",
      "orcid": "0000-0003-2191-3485"
    },
    {
      "affs": [
        2
      ],
      "name": "Alvin Chandra",
      "orcid": "0000-0003-1753-1644"
    },
    {
      "affs": [
        2
      ],
      "name": "Mark H. Drazner",
      "orcid": "0000-0003-3054-4757"
    },
    {
      "affs": [
        9,
        10
      ],
      "name": "M. Tarique Hussain"
    },
    {
      "affs": [
        3,
        2
      ],
      "name": "Vlad Gabriel Zaha",
      "orcid": "0000-0003-4878-891X"
    },
    {
      "affs": [
        11
      ],
      "name": "Thomas J. Wang",
      "orcid": "0000-0003-4063-6508"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/2vhxyv3zwy6xa.bib",
  "cited_by": 8,
  "doi": "10.1038/s41591-026-04504-5",
  "fulltext_url": null,
  "id": "2vhxyv3zwy6xa",
  "issns": [
    "1078-8956",
    "1546-170X",
    "1744-7933"
  ],
  "landing_url": "https://doi.org/10.1038/s41591-026-04504-5",
  "language": "en",
  "licence": "CC-BY-NC-ND",
  "licence_label": "CC BY-NC-ND",
  "licence_source": "journal",
  "licence_url": "https://creativecommons.org/licenses/by-nc-nd/4.0/",
  "metadata_licence": null,
  "native_subjects": [
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      "2705|Heart Failure Treatment and Management"
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  "pdf_url": "https://www.nature.com/articles/s41591-026-04504-5.pdf",
  "pmcid": "PMC13472951",
  "pmid": "42393373",
  "published": "2026-07-02",
  "publisher": "Nature Portfolio",
  "ris": "https://research.draconitic.com/paper/2vhxyv3zwy6xa.ris",
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      "url": "https://doi.org/10.1038/s41591-026-04504-5"
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  "subjects": [
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      "subfield": "cardiovascular"
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  "title": "Polypill for heart failure with reduced ejection fraction: the POLY-HF randomized trial",
  "title_text": "Polypill for heart failure with reduced ejection fraction: the POLY-HF randomized trial",
  "type": "peer-reviewed",
  "updated_at": "2026-11-03T13:20:37Z",
  "url": "https://research.draconitic.com/paper/2vhxyv3zwy6xa",
  "venue": "Nature Medicine",
  "versions": []
}