PLOS Medicine
2026-06-24
DOI: HASH:bae9024fb69419c0173f7cc15e3b27d3
by Linda Chan, Wanchun Xu, Esther W. Y. Chan, Eric Yuk Fai Wan
Background 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 ≥75 years. Methods and findings 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 ‘nested monthly trials’. In each monthly trial, all type 2 diabetes patients aged ≥60 years with elevated low-density lipoprotein cholesterol (≥2.6 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 (60–74, 75–84, ≥85 years) for analysis, with those aged 60–74 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 75–84 years, a significant reduction in the incidence of CVDs (HR 0.69 (95% CI [0.65, 0.75]; p