{
  "abstract": "Aims: PCSK9 inhibitors reduce major cardiovascular events in randomized trials of atherosclerotic cardiovascular disease (ASCVD), but real‐world neuropsychiatric safety remains uncertain.\n\nMethods: In a propensity score–matched retrospective cohort study using the TriNetX U.S. Federated Research Network, adults with established ASCVD initiating alirocumab or evolocumab between 2017 and 2024 were matched 1:1 to statin‐monotherapy initiators. The 12‐month primary analysis assessed major adverse cardiovascular events (MACE: myocardial infarction, heart failure [HF], ischaemic stroke, all‐cause death), neurodegenerative disease (dementia, Parkinson's disease) and psychiatric disorders (psychosis, bipolar disorder, depression, anxiety), with Bonferroni correction and negative control. Secondary analyses examined individual agents, ASCVD subtypes, statin use, an intensified lipid‐lowering comparator and extended follow‐up.\n\nResults: Among 60 885 matched pairs (mean age 70 years; 61% male), PCSK9 inhibitor therapy was associated with lower 12‐month risks of MACE (HR 0.84, 95% CI 0.80–0.88), myocardial infarction (HR 0.82, 0.79–0.86), HF (HR 0.87, 0.83–0.92) and all‐cause mortality (HR 0.40, 0.37–0.43); ischaemic stroke did not differ. After Bonferroni correction, no neurodegenerative association remained significant. PCSK9 inhibitor use was associated with higher risks of any psychiatric diagnosis (HR 1.33, 1.25–1.42), depression (HR 1.44, 1.28–1.61) and anxiety (HR 1.39, 1.28–1.50), persisting in secondary analyses; negative control outcomes did not differ.\n\nConclusions: PCSK9 inhibitor use was associated with favourable cardiovascular outcomes and no clear neurodegenerative harm, but higher rates of depression and anxiety. Given the observational design and potential residual confounding, statin‐intolerance‐related treatment selection and surveillance bias, these findings should be interpreted as hypothesis‐generating and warrant further prospective evaluation.",
  "abstract_shown": true,
  "affiliations": [
    "Liverpool Centre for Cardiovascular Science at University of Liverpool Liverpool John Moores University and Liverpool Heart and Chest Hospital Liverpool UK",
    "Tianjin Key Laboratory of Ionic‐Molecular Function of Cardiovascular disease, Department of Cardiology, Tianjin Institute of Cardiology The Second Hospital of Tianjin Medical University Tianjin China",
    "Department of Cardiovascular and Metabolic Medicine University of Liverpool Liverpool UK",
    "Liverpool Centre for Cardiovascular Sciences University of Liverpool and Liverpool University Hospitals NHS Foundation Trust Liverpool UK",
    "Centre for Biomechanics and Rehabilitation Technologies Staffordshire University Stoke‐on‐Trent UK",
    "Department of Clinical Medicine Aalborg University Aalborg Denmark",
    "Department of Cardiology, Lipidology and Internal Medicine with Intensive Coronary Care Unit Medical University of Bialystok Bialystok Poland"
  ],
  "article_type": "research article",
  "arxiv": null,
  "author_total": 8,
  "authors": [
    {
      "affs": [
        0,
        1
      ],
      "name": "Tianshu Gu",
      "orcid": "0000-0002-8200-4093"
    },
    {
      "affs": [
        0
      ],
      "name": "Yang Chen"
    },
    {
      "affs": [
        1
      ],
      "name": "Nan Zhang"
    },
    {
      "affs": [
        2,
        3,
        4
      ],
      "name": "Uazman Alam"
    },
    {
      "affs": [
        0
      ],
      "name": "Riccardo Proietti"
    },
    {
      "affs": [
        1
      ],
      "name": "Tong Liu",
      "orcid": "0000-0003-0482-0738"
    },
    {
      "affs": [
        1
      ],
      "name": "Kang‐Yin Chen"
    },
    {
      "affs": [
        0,
        1,
        5,
        6
      ],
      "name": "Gregory Y. H. Lip"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/f97x677zqg1wk.bib",
  "cited_by": 0,
  "doi": "10.1002/bcp.70687",
  "fulltext_url": "https://pmc.ncbi.nlm.nih.gov/articles/PMC13714615/",
  "id": "f97x677zqg1wk",
  "issns": [
    "0306-5251",
    "1365-2125"
  ],
  "landing_url": "https://doi.org/10.1002/bcp.70687",
  "language": "en",
  "licence": "CC-BY-4.0",
  "licence_label": "CC BY 4.0",
  "licence_source": "article",
  "licence_url": "https://creativecommons.org/licenses/by/4.0/",
  "metadata_licence": null,
  "native_subjects": [
    [
      "heading",
      "Original Article"
    ],
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      "openalex",
      "2746|Lipoproteins and Cardiovascular Health"
    ]
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  "openalex": "W7167635178",
  "pdf_url": null,
  "pmcid": "PMC13714615",
  "pmid": "42414099",
  "published": "2026-07-07",
  "publisher": null,
  "ris": "https://research.draconitic.com/paper/f97x677zqg1wk.ris",
  "sources": [
    {
      "first_seen": "2026-11-01T12:22:04Z",
      "native_id": "PMC13714615",
      "source": "pmc",
      "url": "https://doi.org/10.1002/bcp.70687"
    }
  ],
  "subjects": [
    {
      "field": "medicine",
      "origin": "openalex:2746|Lipoproteins and Cardiovascular Health",
      "subfield": "surgery"
    }
  ],
  "title": "Cardiovascular and neuropsychiatric outcomes with PCSK9 inhibitors in atherosclerotic cardiovascular disease: A retrospective cohort study",
  "title_text": "Cardiovascular and neuropsychiatric outcomes with PCSK9 inhibitors in atherosclerotic cardiovascular disease: A retrospective cohort study",
  "type": "peer-reviewed",
  "updated_at": "2026-11-01T12:22:04Z",
  "url": "https://research.draconitic.com/paper/f97x677zqg1wk",
  "venue": "British Journal of Clinical Pharmacology",
  "versions": []
}