{
  "abstract": "BackgroundSeveral disease-modifying agents for transthyretin amyloid cardiomyopathy (ATTR-CM) have been investigated, but differences in trial design and background stabilizer use complicate interpretation of their efficacy. This meta-analysis assessed their efficacy overall and by background stabilizer use.\n\nMethodsPubMed, Embase, and the Cochrane Library were searched through September 2026 for phase III randomized, placebo-controlled trials of disease-modifying therapy in ATTR-CM. Primary endpoints were all-cause mortality, 6-minute walk distance (6MWD), Kansas City Cardiomyopathy Questionnaire-Overall Summary (KCCQ-OS) score, and N-terminal pro-B-type natriuretic peptide (NT-proBNP), pooled with a random-effects model. Treatment effects were compared between the monotherapy and baseline stabilizer strata using a mixed-effects model.\n\nResultsFive trials (ATTR-ACT, APOLLO-B, ATTRibute-CM, HELIOS-B, CARDIO-TTRansform; N=3497) were included. Disease-modifying therapy reduced all-cause mortality (risk ratio, 0.76; 95% confidence interval [CI], 0.66-0.87; I2=0%) and improved 6MWD (pooled standardized mean difference [SMD], 0.43; 95% CI, 0.20-0.67), KCCQ-OS score (SMD, 0.37; 95% CI, 0.19-0.55), and NT-proBNP (SMD, - 0.53; 95% CI, -0.89 to -0.18). The mortality benefit was similar whether therapy was given alone or added to a background stabilizer (pooled risk ratio, 0.77 vs. 0.71; P for interaction = 0.59), but treatment effects on 6MWD (pooled SMD, 0.49 vs. 0.14), KCCQ-OS score (0.44 vs. 0.07), and NT-proBNP (-0.65 vs. -0.13) were smaller among patients receiving a background stabilizer (P for interaction = 0.012, <0.001, and 0.029, respectively).\n\nConclusionDisease-modifying treatments reduced all-cause mortality and favored functional capacity, health status, and NT-proBNP outcomes in patients with ATTR-CM. Exploratory subgroup analyses showed smaller treatment effects on 6MWD, KCCQ-OS score, and NT-proBNP among patients receiving a background stabilizer, with no statistically significant difference in the mortality effect according to baseline stabilizer use.\n\nWhat Is New?O_LIThis meta-analysis of all five phase III randomized controlled trials of disease-modifying therapy in transthyretin amyloid cardiomyopathy (3497 analyzed participants) found a lower risk of all-cause mortality (risk ratio, 0.76; 95% CI, 0.66-0.87) and more favorable 6-minute walk distance, Kansas City Cardiomyopathy Questionnaire-Overall Summary score, and N-terminal pro-B-type natriuretic peptide (NT-proBNP). C_LIO_LIIn subgroup analyses, the mortality effect was similar with and without a background transthyretin stabilizer at randomization, whereas effects on functional capacity, health status, and NT-proBNP were smaller among patients receiving a background stabilizer. C_LI\n\nWhat Are the Clinical Implications?O_LIAmong patients already receiving a transthyretin stabilizer, adding a second agent was associated with a mortality reduction similar to that seen without background therapy but with smaller incremental gains in functional and biomarker outcomes; because these findings rest on aggregate trial data and subgroup comparisons, they should be interpreted cautiously. C_LI",
  "abstract_shown": true,
  "affiliations": [
    "National Taiwan University College of Medicine and Hospital"
  ],
  "article_type": "PUBLISHAHEADOFPRINT",
  "arxiv": null,
  "author_total": 9,
  "authors": [
    {
      "name": "Y.-H. Hung"
    },
    {
      "name": "C.-H. Tsai"
    },
    {
      "name": "T.-W. Kao"
    },
    {
      "name": "Y.-W. Wu"
    },
    {
      "name": "W.-C. Yu"
    },
    {
      "name": "S. Carigi"
    },
    {
      "name": "B. W. Sperry"
    },
    {
      "name": "S. Perlini"
    },
    {
      "affs": [
        0
      ],
      "name": "Y.-H. Lin"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/fa66xg84tzbd3.bib",
  "cited_by": 0,
  "doi": "10.64898/2026.10.10.26365208",
  "fulltext_url": "https://www.medrxiv.org/content/10.64898/2026.10.10.26365208v1.full",
  "id": "fa66xg84tzbd3",
  "issns": [],
  "landing_url": "https://www.medrxiv.org/content/10.64898/2026.10.10.26365208v1",
  "language": null,
  "licence": "CC-BY-NC-ND",
  "licence_label": "CC BY-NC-ND",
  "licence_source": "article",
  "licence_url": "https://creativecommons.org/licenses/by-nc-nd/4.0/",
  "metadata_licence": null,
  "native_subjects": [
    [
      "medrxiv",
      "cardiovascular medicine"
    ],
    [
      "openalex",
      "1312|Amyloidosis: Diagnosis, Treatment, Outcomes"
    ]
  ],
  "openalex": "W7221577828",
  "pdf_url": "https://www.medrxiv.org/content/10.64898/2026.10.10.26365208v1.full.pdf",
  "pmcid": null,
  "pmid": null,
  "published": "2026-10-10",
  "publisher": null,
  "ris": "https://research.draconitic.com/paper/fa66xg84tzbd3.ris",
  "sources": [
    {
      "first_seen": "2026-10-30T12:20:44Z",
      "native_id": "10.64898/2026.10.10.26365208",
      "source": "medrxiv",
      "url": "https://www.medrxiv.org/content/10.64898/2026.10.10.26365208v1"
    }
  ],
  "subjects": [
    {
      "field": "medicine",
      "origin": "medrxiv:cardiovascular medicine",
      "subfield": "cardiovascular"
    }
  ],
  "title": "Efficacy of Disease-Modifying Treatments in Transthyretin Amyloid Cardiomyopathy: A Systematic Review and Meta-Analysis of Five Phase III Randomized Controlled Trials",
  "title_text": "Efficacy of Disease-Modifying Treatments in Transthyretin Amyloid Cardiomyopathy: A Systematic Review and Meta-Analysis of Five Phase III Randomized Controlled Trials",
  "type": "preprint",
  "updated_at": "2026-10-30T12:20:44Z",
  "url": "https://research.draconitic.com/paper/fa66xg84tzbd3",
  "venue": "medRxiv",
  "versions": []
}