{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,24]],"date-time":"2026-06-24T17:51:30Z","timestamp":1782323490219,"version":"3.54.5"},"reference-count":49,"publisher":"Public Library of Science (PLoS)","issue":"6","license":[{"start":{"date-parts":[[2026,6,24]],"date-time":"2026-06-24T00:00:00Z","timestamp":1782259200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"crossref","id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/501100010909","name":"Excellent Young Scientists Fund","doi-asserted-by":"publisher","award":["82222902"],"award-info":[{"award-number":["82222902"]}],"id":[{"id":"10.13039\/501100010909","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Health and Medical Research Fund from Health Bureau of the Government of the Hong Kong","award":["05190107 and 22233101"],"award-info":[{"award-number":["05190107 and 22233101"]}]}],"content-domain":{"domain":["www.plosmedicine.org"],"crossmark-restriction":false},"short-container-title":["PLoS Med"],"abstract":"<jats:sec id=\"sec001\">\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>There is limited evidence on the use of statins for primary prevention of cardiovascular disease (CVD) in older adults with type 2 diabetes due to underrepresentation of this population in randomized controlled trials (RCTs). We aimed to determine the effectiveness and safety of statin therapy for primary CVD prevention among type 2 diabetes patients aged \u226575 years.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec id=\"sec002\">\n                    <jats:title>Methods and findings<\/jats:title>\n                    <jats:p>\n                      In this cohort study, territory-wide electronic health records (EHRs) from the Hospital Authority Clinical Management System in Hong Kong were used to emulate a sequence of nested target trials. Eligible patients were included in a rolling basis in each calendar month from January 2009 to December 2015, and thus we emulated 84 \u2018nested monthly trials\u2019. In each monthly trial, all type 2 diabetes patients aged \u226560 years with elevated low-density lipoprotein cholesterol (\u22652.6 mmol\/L) in the baseline calendar month were included; patients with a history of type 1 diabetes, CVDs, cancers, muscle-related disorders, or liver dysfunction were excluded from analysis. Eligible individuals were classified into statin initiators or noninitiators based on whether they initiated statin therapy at the time of enrollment. They were categorized into various age groups (60\u201374, 75\u201384,\u2009\u226585 years) for analysis, with those aged 60\u201374 years forming a benchmark group to test the validity of the emulated target trial. Patients were followed up until the outcome of interest, death, or the administrative end (December 2018), whichever occurred first. We estimated hazard ratios (HRs) comparing statin use versus nonuse for CVDs, all-cause mortality, muscle-related adverse events (AEs), and liver dysfunction using pooled logistic models, with inverse probability weighting to adjust for time-varying confounders related to treatment adherence, under the assumption of no unmeasured confounding. Propensity score matching was performed on eligible person-trials at baseline, incorporating demographic characteristics, clinical and laboratory parameters, comorbidities, medication history, and healthcare utilization as matching variables. Among 30,804 matched person-trials aged 75\u201384 years, a significant reduction in the incidence of CVDs (HR 0.69 (95% CI [0.65, 0.75];\n                      <jats:italic>p<\/jats:italic>\n                      \u2009&lt;\u20090.001)) and all-cause mortality (0.65 [0.60, 0.70],\n                      <jats:italic>p<\/jats:italic>\n                      \u2009&lt;\u20090.001) was observed. In 3,798 matched person-trials aged \u226585 years, the benefits were consistently observed (CVDs: 0.65 [0.54, 0.77],\n                      <jats:italic>p<\/jats:italic>\n                      \u2009&lt;\u20090.001; all-cause mortality: 0.61 [0.52, 0.71],\n                      <jats:italic>p<\/jats:italic>\n                      \u2009&lt;\u20090.001). No substantially increased risks for muscle-related AEs or liver dysfunction were observed in both age groups. The effectiveness and safety of statins for the benchmark age group (60\u201374 years) were also confirmed. The remaining source of bias included the potential misclassification bias due to reliance on diagnosis coding in EHRs, as well as unmeasured confounding relating to lifestyle factors, social determinants, and information on the shared decision-making between physicians and patients.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec id=\"sec003\">\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>In type 2 diabetes patients aged \u226575 years, we found that statin use was associated with reduced risks of CVDs and all-cause mortality, including those aged over 85 years. No substantially increased risks for muscle-related adverse events and liver dysfunction were observed. Future studies, including RCTs, are warranted to confirm the effectiveness and safety of statin use in older adults with diabetes, and to determine optimal statin dosing and the comparative efficacy of different statin types, thereby improving CVD prevention in this population.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1371\/journal.pmed.1005136","type":"journal-article","created":{"date-parts":[[2026,6,24]],"date-time":"2026-06-24T17:27:24Z","timestamp":1782322044000},"page":"e1005136","update-policy":"https:\/\/doi.org\/10.1371\/journal.pmed.corrections_policy","source":"Crossref","is-referenced-by-count":0,"title":["Cardiovascular outcomes and safety associated with statin therapy for primary prevention in older adults with type 2 diabetes: A target trial emulation study"],"prefix":"10.1371","volume":"23","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-9802-5059","authenticated-orcid":true,"given":"Linda","family":"Chan","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wanchun","family":"Xu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7602-9470","authenticated-orcid":true,"given":"Esther W. Y.","family":"Chan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6275-1147","authenticated-orcid":true,"given":"Eric Yuk Fai","family":"Wan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"340","published-online":{"date-parts":[[2026,6,24]]},"reference":[{"key":"pmed.1005136.ref001","unstructured":"World Health Organization. World Health Statistics 2023: a visual summary. 2023. 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