{
  "abstract": "Dual antiplatelet therapy (DAPT) reduces stroke recurrence after minor stroke/TIA, yet a clinically meaningful proportion of patients remain functionally dependent at 90 days. We developed an interpretable clinical prediction model to define a high-risk subgroup, and separately explored pharmacogenetic associations within this subgroup to generate hypotheses for precision secondary prevention. In this post-hoc analysis of the INSPIRES trial (4,439 patients), LASSO logistic regression selected predictors for 90-day functional dependence (mRS > 2). Model performance was assessed by discrimination, calibration, and decision curve analysis. In a genotyped subcohort, CYP1A2 rs762551 and POR rs1057868 were evaluated for outcome association and enrichment in the high-risk subgroup. Logistic regression achieved the highest AUC point estimate (AUC = 0.727) among the four models evaluated (AUC range: 0.495-0.698; 95% CIs overlapped across models); it was selected as the final model for its interpretability and calibration, rather than for statistical superiority. Key predictors were admission NIHSS, age >65 years, and diabetes. The highest-risk quartile (25% of patients) carried a disproportionate outcome burden, with no effect modification by antiplatelet strategy (p = 0.793). CYP1A2 CC (23.65% vs. 16.28%; Pearson χ2p = 0.0031) and POR TC (54.58% vs. 46.22%; Pearson χ2p = 0.0105) genotypes were enriched in functionally dependent patients; CYP1A2 showed no significant allele-dosage trend (trend p = 0.0821), whereas POR demonstrated a significant allele-dosage trend (p = 0.0032). This clinical prediction model identified a high-risk subgroup accounting for most poor outcomes after minor stroke/TIA. Exploratory analyses identified CYP1A2 and POR variants enriched in this subgroup, generating pharmacogenetic hypotheses for future investigation.",
  "abstract_shown": true,
  "affiliations": [
    "Beijing Tiantan Hospital, Capital Medical University, Beijing, China.",
    "Department of Neurology, Beijing Tiantan Hospital, Capital Medical University, Beijing, China.",
    "China National Clinical Research Center for Neurological Diseases, Beijing, China.",
    "Chinese Institute for Brain Research, Beijing, China.",
    "National Center for Neurological Disorders, Beijing, China.",
    "Advanced Innovation Center for Human Brain Protection, Capital Medical University, Beijing, China.",
    "Beijing Laboratory of Oral Health, Capital Medical University, Beijing, China.",
    "Laboratory for Clinical Medicine, Capital Medical University, Beijing, China."
  ],
  "article_type": "research article",
  "arxiv": null,
  "author_total": 6,
  "authors": [
    {
      "affs": [
        0
      ],
      "name": "Yaping Wang"
    },
    {
      "affs": [
        0
      ],
      "name": "Baizhu Li"
    },
    {
      "affs": [
        1,
        2
      ],
      "name": "Hongyi Yan"
    },
    {
      "affs": [
        2
      ],
      "name": "Lingling Jiang"
    },
    {
      "affs": [
        1,
        2
      ],
      "name": "Yuesong Pan"
    },
    {
      "affs": [
        1,
        2,
        3,
        4,
        5,
        6,
        7
      ],
      "name": "Yilong Wang"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/5xqhhq9kk98fb.bib",
  "cited_by": 0,
  "doi": "10.3389/fnagi.2026.1922100",
  "fulltext_url": "https://europepmc.org/articles/PMC13713692",
  "id": "5xqhhq9kk98fb",
  "issns": [
    "1663-4365"
  ],
  "landing_url": "https://europepmc.org/article/MED/42953014",
  "language": "eng",
  "licence": "CC-BY",
  "licence_label": "CC BY",
  "licence_source": "article",
  "licence_url": "https://creativecommons.org/licenses/by/4.0/",
  "metadata_licence": null,
  "native_subjects": [
    [
      "heading",
      "Original Research"
    ],
    [
      "openalex",
      "2713|Acute Ischemic Stroke Management"
    ]
  ],
  "openalex": "W7221827442",
  "pdf_url": "https://europepmc.org/articles/PMC13713692?pdf=render",
  "pmcid": "PMC13713692",
  "pmid": "42953014",
  "published": "2026-10-14",
  "publisher": "Frontiers Media SA",
  "ris": "https://research.draconitic.com/paper/5xqhhq9kk98fb.ris",
  "sources": [
    {
      "first_seen": "2026-10-31T00:20:41Z",
      "native_id": "MED:42953014",
      "source": "europepmc",
      "url": "https://europepmc.org/article/MED/42953014"
    },
    {
      "first_seen": "2026-10-31T12:24:12Z",
      "native_id": "PMC13713692",
      "source": "pmc",
      "url": "https://doi.org/10.3389/fnagi.2026.1922100"
    }
  ],
  "subjects": [
    {
      "field": "medicine",
      "origin": "openalex:2713|Acute Ischemic Stroke Management",
      "subfield": "epidemiology-public-health"
    }
  ],
  "title": "A clinical prediction model for 90-day functional dependence after minor stroke/TIA with exploratory pharmacogenetic associations: a post-hoc analysis of the INSPIRES trial.",
  "title_text": "A clinical prediction model for 90-day functional dependence after minor stroke/TIA with exploratory pharmacogenetic associations: a post-hoc analysis of the INSPIRES trial.",
  "type": "peer-reviewed",
  "updated_at": "2026-11-01T12:21:19Z",
  "url": "https://research.draconitic.com/paper/5xqhhq9kk98fb",
  "venue": "Frontiers in aging neuroscience",
  "versions": []
}