{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,8]],"date-time":"2026-07-08T02:16:39Z","timestamp":1783476999196,"version":"3.55.0"},"reference-count":34,"publisher":"Wiley","license":[{"start":{"date-parts":[[2026,7,7]],"date-time":"2026-07-07T00:00:00Z","timestamp":1783382400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2026,7,7]],"date-time":"2026-07-07T00:00:00Z","timestamp":1783382400000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Br J Clin Pharmacol"],"abstract":"<jats:sec>\n                    <jats:title>Aims<\/jats:title>\n                    <jats:p>PCSK9 inhibitors reduce major cardiovascular events in randomized trials of atherosclerotic cardiovascular disease (ASCVD), but real\u2010world neuropsychiatric safety remains uncertain.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>In a propensity score\u2013matched 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\u2010monotherapy initiators. The 12\u2010month primary analysis assessed major adverse cardiovascular events (MACE: myocardial infarction, heart failure [HF], ischaemic stroke, all\u2010cause 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\u2010lowering comparator and extended follow\u2010up.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>Among 60\u2009885 matched pairs (mean age 70\u2009years; 61% male), PCSK9 inhibitor therapy was associated with lower 12\u2010month risks of MACE (HR 0.84, 95% CI 0.80\u20130.88), myocardial infarction (HR 0.82, 0.79\u20130.86), HF (HR 0.87, 0.83\u20130.92) and all\u2010cause mortality (HR 0.40, 0.37\u20130.43); 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\u20131.42), depression (HR 1.44, 1.28\u20131.61) and anxiety (HR 1.39, 1.28\u20131.50), persisting in secondary analyses; negative control outcomes did not differ.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>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\u2010intolerance\u2010related treatment selection and surveillance bias, these findings should be interpreted as hypothesis\u2010generating and warrant further prospective evaluation.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/bcp.70687","type":"journal-article","created":{"date-parts":[[2026,7,8]],"date-time":"2026-07-08T01:34:41Z","timestamp":1783474481000},"source":"Crossref","is-referenced-by-count":0,"title":["Cardiovascular and neuropsychiatric outcomes with PCSK9 inhibitors in atherosclerotic cardiovascular disease: A retrospective cohort study"],"prefix":"10.1002","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-8200-4093","authenticated-orcid":false,"given":"Tianshu","family":"Gu","sequence":"first","affiliation":[{"name":"Liverpool Centre for Cardiovascular Science at University of Liverpool Liverpool John Moores University and Liverpool Heart and Chest Hospital  Liverpool UK"},{"name":"Tianjin Key Laboratory of Ionic\u2010Molecular Function of Cardiovascular disease, Department of Cardiology, Tianjin Institute of Cardiology The Second Hospital of Tianjin Medical University  Tianjin China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yang","family":"Chen","sequence":"additional","affiliation":[{"name":"Liverpool Centre for Cardiovascular Science at University of Liverpool Liverpool John Moores University and Liverpool Heart and Chest Hospital  Liverpool UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nan","family":"Zhang","sequence":"additional","affiliation":[{"name":"Tianjin Key Laboratory of Ionic\u2010Molecular Function of Cardiovascular disease, Department of Cardiology, Tianjin Institute of Cardiology The Second Hospital of Tianjin Medical University  Tianjin China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Uazman","family":"Alam","sequence":"additional","affiliation":[{"name":"Department of Cardiovascular and Metabolic Medicine University of Liverpool  Liverpool UK"},{"name":"Liverpool Centre for Cardiovascular Sciences University of Liverpool and Liverpool University Hospitals NHS Foundation Trust  Liverpool UK"},{"name":"Centre for Biomechanics and Rehabilitation Technologies Staffordshire University  Stoke\u2010on\u2010Trent UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Riccardo","family":"Proietti","sequence":"additional","affiliation":[{"name":"Liverpool Centre for Cardiovascular Science at University of Liverpool Liverpool John Moores University and Liverpool Heart and Chest Hospital  Liverpool UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0482-0738","authenticated-orcid":false,"given":"Tong","family":"Liu","sequence":"additional","affiliation":[{"name":"Tianjin Key Laboratory of Ionic\u2010Molecular Function of Cardiovascular disease, Department of Cardiology, Tianjin Institute of Cardiology The Second Hospital of Tianjin Medical University  Tianjin China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kang\u2010Yin","family":"Chen","sequence":"additional","affiliation":[{"name":"Tianjin Key Laboratory of Ionic\u2010Molecular Function of Cardiovascular disease, Department of Cardiology, Tianjin Institute of Cardiology The Second Hospital of Tianjin Medical University  Tianjin China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gregory Y. 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