{
  "abstract": "Background: In transthyretin amyloid cardiomyopathy (ATTR-CM), treatment effects are often delayed and stage-dependent, which complicates interpretation of a single HR. The timing of relative and absolute benefit at each stage is unclear. We examined stage-specific treatment effects of tafamidis using complementary time-to-event analyses.\n\nMethods: Individual patient-level data were reconstructed from published Kaplan-Meier curves of the Tafamidis in Transthyretin Cardiomyopathy Clinical Trial long-term extension and analysed by National Amyloidosis Centre (NAC) stage. Time to benefit (TTB) was estimated from flexible parametric (Royston-Parmar) models with time-varying treatment effects, providing time-varying HRs and absolute risk reduction and was cross-checked with truncated Cox and restricted mean survival time (RMST) trajectory analyses.\n\nResults: Effects differed by NAC stage. Tafamidis reduced mortality in NAC1 (HR 0.45, 95% CI 0.27 to 0.73) and NAC2 (HR 0.55, 95% CI 0.35 to 0.86); no effect was seen in NAC3. Hazard reduction was early and consistent in NAC1 but delayed in NAC2. HR-based TTB was 36 months in NAC1 and 50 months in NAC2 and was not reached in NAC3. RMST-based TTB occurred later (38 and 61 months). At maximum follow-up, RMST gain was 17 months in NAC1, 13 months in NAC2 and 1 month in NAC3.\n\nConclusions: Survival benefit from tafamidis is stage-dependent, appearing earlier and lasting longer in less advanced disease. In intermediate-stage disease, relative effects preceded—and at times diverged from—absolute survival gains. These data support early initiation of therapy and the use of complementary analytical approaches alongside the conventional HR.",
  "abstract_shown": true,
  "affiliations": [
    "Cardiovascular Medicine, Saga University Faculty of Medicine Graduate School of Medical Sciences, Saga, Japan",
    "Saga University Faculty of Medicine Graduate School of Medical Sciences, Saga, Japan",
    "Department of Cardiovascular Medicine, Tobata General Hospital, Kitakyushu, Fukuoka Prefecture, Japan"
  ],
  "article_type": "research article",
  "arxiv": null,
  "author_total": 5,
  "authors": [
    {
      "affs": [
        0
      ],
      "name": "Yosuke Nabeshima",
      "orcid": "0000-0003-4329-2819"
    },
    {
      "affs": [
        0
      ],
      "name": "Tetsuya Kaneko"
    },
    {
      "affs": [
        0
      ],
      "name": "Ayumu Yajima"
    },
    {
      "affs": [
        1
      ],
      "name": "Koichi Node"
    },
    {
      "affs": [
        2
      ],
      "name": "Masaaki Takeuchi",
      "orcid": "0000-0001-7606-1537"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/2kvrc2zvhrsk0.bib",
  "cited_by": 0,
  "doi": "10.1136/openhrt-2026-004295",
  "fulltext_url": "https://pmc.ncbi.nlm.nih.gov/articles/PMC13711599/",
  "id": "2kvrc2zvhrsk0",
  "issns": [
    "2053-3624"
  ],
  "landing_url": "https://doi.org/10.1136/openhrt-2026-004295",
  "language": "en",
  "licence": "CC-BY-NC-4.0",
  "licence_label": "CC BY-NC 4.0",
  "licence_source": "article",
  "licence_url": "https://creativecommons.org/licenses/by-nc/4.0/",
  "metadata_licence": null,
  "native_subjects": [
    [
      "heading",
      "1506"
    ],
    [
      "heading",
      "Heart Failure and Cardiomyopathies"
    ],
    [
      "heading",
      "Original Research"
    ],
    [
      "openalex",
      "1312|Amyloidosis: Diagnosis, Treatment, Outcomes"
    ]
  ],
  "openalex": "W7223707615",
  "pdf_url": null,
  "pmcid": "PMC13711599",
  "pmid": "42933877",
  "published": "2026-10-26",
  "publisher": "BMJ Publishing Group",
  "ris": "https://research.draconitic.com/paper/2kvrc2zvhrsk0.ris",
  "sources": [
    {
      "first_seen": "2026-10-31T12:22:21Z",
      "native_id": "PMC13711599",
      "source": "pmc",
      "url": "https://doi.org/10.1136/openhrt-2026-004295"
    }
  ],
  "subjects": [
    {
      "field": "biochemistry",
      "origin": "openalex:1312|Amyloidosis: Diagnosis, Treatment, Outcomes",
      "subfield": "molecular-biology"
    }
  ],
  "title": "Stage-dependent timing of relative and absolute treatment benefit in transthyretin amyloid cardiomyopathy",
  "title_text": "Stage-dependent timing of relative and absolute treatment benefit in transthyretin amyloid cardiomyopathy",
  "type": "peer-reviewed",
  "updated_at": "2026-10-31T12:22:21Z",
  "url": "https://research.draconitic.com/paper/2kvrc2zvhrsk0",
  "venue": "Open Heart",
  "versions": []
}