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dc.contributor.authorTürkmen, D.
dc.contributor.authorMasoli, J. A. H.
dc.contributor.authorKuo, C. L.
dc.contributor.authorBowden, J.
dc.contributor.authorMelzer, D.
dc.contributor.authorPilling, L. C.
dc.date.accessioned2022-04-21T09:41:51Z
dc.date.available2022-04-21T09:41:51Z
dc.date.issued2022-01-26
dc.identifier.citationBr J Clin Pharmacol. 2022 Jan 26. doi: 10.1111/bcp.15245.
dc.identifier.pmid35083771
dc.identifier.doi10.1111/bcp.15245
dc.identifier.urihttps://rde.dspace-express.com/handle/11287/622471
dc.description.abstractOBJECTIVE: To estimate the effect of rs4149056 (SLCO1B1*5) genotype (decreases statin transport) on cholesterol control and treatment duration in male and female primary care patients prescribed common statin medications. METHODS AND ANALYSIS: This study comprised 69 185 European-ancestry UK Biobank cohort participants prescribed simvastatin or atorvastatin (aged 40-79 years at first prescription, treatment duration 1 month to 29 years, mean 5.7 years). Principal outcomes were clinically high total cholesterol (>5 mmol/L) at baseline, plus treatment discontinuation. RESULTS: A total of 48.4% of 591 females homozygous for SLCO1B1*5 decreased function genotype had raised cholesterol vs 41.7% of those with functioning SLCO1B1 (odds ratio 1.31, 95% confidence interval [CI] 1.1-1.55, P = .001). Fewer males had high cholesterol and the genotype effect was attenuated. In primary care prescribing, females homozygous for SLCO1B1*5 were more likely to stop receiving these statins (29.5%) than women with normal SLCO1B1 (25.7%) (hazard ratio [HR] 1.19, 95% CI 1.03-1.37, P = .01), amounting to five discontinuations per 100 statin-years in the SLCO1B1*5 group vs four in the normal SLCO1B1 function group. This remained significant after the first year of treatment (HR for discontinuing >1 year after first prescription 1.3, 95% CI 1.08-1.56, P = .006). In men SLCO1B1*5 was only associated with treatment discontinuation in the first year. CONCLUSIONS: In this large community sample of patients on commonly prescribed statins, the SLCO1B1*5 decreased function variant had much larger effects on cholesterol control and treatment duration in women than in men. Efforts to improve the effectiveness of statin therapy in women may need to include SLCO1B1*5 genotype-guided statin selection.
dc.language.isoeng
dc.publisherWiley
dc.relation.urlhttps://doi.org/10.1111/bcp.15245
dc.rights© 2022 The Authors. British Journal of Clinical Pharmacology published by John Wiley & Sons Ltd on behalf of British Pharmacological Society.
dc.rights.urihttp://creativecommons.org/publicdomain/zero/1.0/
dc.subjectepidemiology
dc.subjectgenetics
dc.subjectpharmacogenomics
dc.subjectprimary care
dc.subjectstatins
dc.titleStatin treatment effectiveness and the SLCO1B1*5 reduced function genotype: Long-term outcomes in women and men
dc.typeJournal Article
dc.identifier.journalBritish journal of clinical pharmacology
dc.description.noteThe article is available via Open Access. Click on the 'Additional link' above to access the full-text.
dc.type.versionaheadofprint
dc.description.admin-noteAccepted version (6 month embargo), submitted version
dc.date.epub2022-01-28


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© 2022 The Authors. British Journal of Clinical Pharmacology published by John Wiley & Sons Ltd on behalf of British Pharmacological Society.
Except where otherwise noted, this item's license is described as © 2022 The Authors. British Journal of Clinical Pharmacology published by John Wiley & Sons Ltd on behalf of British Pharmacological Society.