{
  "abstract": "Background: Oral anticoagulation (OAC) reduces stroke risk in patients with atrial fibrillation (AF), and screening can enable earlier AF detection and OAC initiation. However, the population-level trade-off between stroke prevention and OAC-related major bleeding for different types of AF and OAC therapy remains uncertain, and large randomized trials to resolve this are costly and time-consuming. Methods: A state-transition Markov-like model was developed to: 1) simulate the lifetime course of AF, stroke, major bleeding, and death in different virtual populations; 2) quantify benefits (stroke reduction) and harms (major bleeding) of systematic AF screening with screening-triggered OAC across CHA2DS2-VA scores; and 3) compare rhythm-guided, time-delimited (\"pill-in-pocket\") OAC with continuous OAC. Results: The model synthesized information from multiple clinical sources and reproduced stroke and bleeding incidence across clinical scenarios. At CHA?DS?-VA=2, long-term continuous rhythm monitoring (LT-CRM) with OAC lowered stroke risk (HR, 0.92 [95%CI, 0.88-0.96]) but raised bleeding risk (HR, 1.17 [95%CI, 1.07-1.27]) versus no screening. Time-to-benefit was shorter than time-to-harm for CHA?DS?-VA?4, but longer for CHA?DS?-VA=0. Pill-in-pocket OAC vs continuous OAC showed no difference in stroke/mortality (HR, 1.03, 95%CI [0.91-1.16]) but lower bleeding risk (HR, 0.81, 95%CI: 0.68-0.96]) in patients with elevated bleeding risk, but not at baseline. Sensitivity analyses revealed that the risk-benefit profiles of screening or pill-in-pocket OAC strategy further depend on OAC adherence and bleeding risks. Conclusions: Our model highlights a trade-off between stroke reduction and bleeding for systematic screening-initiated OAC, with net benefit for CHA?DS?-VA?4. We provide the first virtual implementation of an ongoing rhythm-guided OAC trial, showing that pill-in-pocket OAC may lower bleeding risk compared to continuous OAC, highlighting the potential of virtual clinical trials to guide clinical trial design.",
  "abstract_shown": true,
  "affiliations": [
    "Medizinische Universitat Graz"
  ],
  "article_type": "PUBLISHAHEADOFPRINT",
  "arxiv": null,
  "author_total": 7,
  "authors": [
    {
      "name": "M. Cai"
    },
    {
      "name": "F. Farahani"
    },
    {
      "name": "M. Rienstra"
    },
    {
      "name": "S. Severi"
    },
    {
      "name": "H. J. G. M. Crijns"
    },
    {
      "name": "U. Schotten"
    },
    {
      "affs": [
        0
      ],
      "name": "J. Heijman"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/9dvhpnjctw7f9.bib",
  "cited_by": 0,
  "doi": "10.64898/2026.11.04.26367324",
  "fulltext_url": "https://www.medrxiv.org/content/10.64898/2026.11.04.26367324v1.full",
  "id": "9dvhpnjctw7f9",
  "issns": [],
  "landing_url": "https://www.medrxiv.org/content/10.64898/2026.11.04.26367324v1",
  "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": null,
  "pdf_url": "https://www.medrxiv.org/content/10.64898/2026.11.04.26367324v1.full.pdf",
  "pmcid": null,
  "pmid": null,
  "published": "2026-11-04",
  "publisher": null,
  "ris": "https://research.draconitic.com/paper/9dvhpnjctw7f9.ris",
  "sources": [
    {
      "first_seen": "2026-11-06T00:21:06Z",
      "native_id": "10.64898/2026.11.04.26367324",
      "source": "medrxiv",
      "url": "https://www.medrxiv.org/content/10.64898/2026.11.04.26367324v1"
    }
  ],
  "subjects": [
    {
      "field": "medicine",
      "origin": "medrxiv:cardiovascular medicine",
      "subfield": "cardiovascular"
    }
  ],
  "title": "Risk-benefit assessment of oral anticoagulation in atrial fibrillation using virtual clinical trials",
  "title_text": "Risk-benefit assessment of oral anticoagulation in atrial fibrillation using virtual clinical trials",
  "type": "preprint",
  "updated_at": "2026-11-07T00:20:53Z",
  "url": "https://research.draconitic.com/paper/9dvhpnjctw7f9",
  "venue": "medRxiv",
  "versions": []
}