Journal Article

Understanding the causes and consequences of low statin adherence: evidence from UK Biobank primary care data

Türkmen, Deniz, Masoli, Jane A. H., Gill, Dipender, Bowden, Jack, Liang, Xiaoran, Pilling, Luke C.

2025

Overview

Background Statins are prescribed to lower LDL cholesterol. Clinical guidelines recommend 30–50% reduction within 3 months, yet many patients do not achieve this. We investigated predictors of LDL-c reduction, treatment adherence, and adverse clinical outcomes in a sample of UK Biobank participants. Methods We analysed 76,000 UK Biobank participants prescribed atorvastatin or simvastatin in primary care: 41,000 had LDL-c measurements before statin initiation (median = 16 days prior, IQR = 28) and within a year of starting treatment (median = 89 days, IQR = 125). Adherence was defined as the “proportion of days covered” (PDC). We estimated associations between PDC within 1 year of statin initiation, genetic factors, post-treatment LDL-c reduction, and clinical adverse outcomes. For 13,000 patients with ≥ 3 LDL-c measures, we used inverse probability of treatment weighting methods to estimate the effect of sustained adherence intervention on LDL-c reduction longitudinally. Results LDL-c reduction following statin initiation was predicted by time until the 1st measurement (up to 26% greater reduction if returned ≤ 3 months vs > 3 months), PDC (up to 38% reduction when PDC > 95% [high] vs. 15% when PDC < 50% [low]), and the pharmacogenetic variant SLCO1B1 *5 (lowest reduction in CC-allele: 37% versus TT-allele: 39.5%). Longitudinal causal modelling showed that the most recent PDC measure exerted the largest influence on overall LDL-c reduction, followed by the initial PDC. Genetic predictors of reduced PDC included liability to schizophrenia (Coef top 20%  − 1.94, 95%CI − 2.69 to − 1.19), while genetic liability to cardiovascular diseases increased PDC (Coef top 20% 1.30, 95%CI 0.55 to 2.05). High PDC was associated with increased risk of incident iron deficiency anaemia (HR 1.30, 95%CI 1.09–1.54) and cataract (HR 1.20, 95%CI 1.07–1.34), and decreased risk of incident coronary heart disease (HR 0.78, 95%CI 0.73–0.84). Conclusions We identify substantial variability in the time to first on-treatment LDL-c measurements and also in adherence to statin medication, highlighting a gap between NHS guidelines, LDL-c monitoring, and statin adherence. We show its subsequent impact on long-term health, demonstrating the potential effect of targeted interventions to improve adherence. We identify important predictors of reduced statin effectiveness, including pharmacogenetic variants, polygenic scores, but most of all, adherence. Tailored statin therapy strategies with patient education on statin indication and adherence could optimize treatment efficacy, safety, and long-term clinical outcomes.

• Publisher: BioMed Central,BioMed Central Ltd,Springer Nature B.V,BMC
• Subject: Adherence / Aged / Alleles / Analysis / Analysis and chemistry / Anemia / Aortic aneurysms / Atorvastatin / Atorvastatin - therapeutic use / Biobanks / Biological Specimen Banks / Biomedicine / Blood / Cardiovascular / Cardiovascular disease / Cardiovascular diseases / Cholesterol / Cholesterol, LDL - blood / Clinical outcomes / Coronary artery disease / Deficiency diseases / Disease prevention / Dosage and administration / Drug dosages / Effectiveness / Female / Genetic factors / Guidelines / Health care / Health risk assessment / Health services / Heart diseases / Humans / Hydroxymethylglutaryl-CoA Reductase Inhibitors - therapeutic use / Iron deficiency / Ischemia / Liability / Lipids / Low density lipoprotein / Male / Medication Adherence / Medicine / Medicine & Public Health / Mental disorders / Middle Aged / Nutrient deficiency / Patient compliance / Patient education / Patients / Pharmacogenomics / Practice guidelines (Medicine) / Prescriptions / Prevention / Primary care / Primary Health Care / Regression analysis / Risk factors / Schizophrenia / Simvastatin / Simvastatin - therapeutic use / Statin / Statins / Stroke / Transient ischemic attack / UK Biobank / United Kingdom / Weighting methods