title: Non-response to (statin) therapy: the importance of distinguishing non-responders from non-adherers in pharmacogenetic studies.
abstract: OBJECTIVE
  In pharmacogenetic research, genetic variation in non-responders and high responders is compared with the aim to identify the genetic loci responsible for this variation in response. However, an important question is whether the non-responders are truly biologically non-responsive or actually non-adherent? Therefore, the aim of this study was to describe, within the PROspective Study of Pravastatin in the Elderly at Risk (PROSPER), characteristics of both non-responders and high responders of statin treatment in order to possibly discriminate non-responders from non-adherers.
  
  
  METHODS
  Baseline characteristics of non-responders to statin therapy (≤10 % LDL-C reduction) were compared with those of high responders (>40 % LDL-C reduction) through a linear regression analysis. In addition, pharmacogenetic candidate gene analysis was performed to show the effect of excluding non-responders from the analysis.
  
  
  RESULTS
  Non-responders to statin therapy were younger (p = 0.001), more often smoked (p < 0.001), had a higher alcohol consumption (p < 0.001), had lower LDL cholesterol levels (p < 0.001), had a lower prevalence of hypertension (p < 0.001), and had lower cognitive function (p = 0.035) compared to subjects who highly responded to pravastatin treatment. Moreover, excluding non-responders from pharmacogenetic studies yielded more robust results, as standard errors decreased.
  
  
  CONCLUSIONS
  Our results suggest that non-responders to statin therapy are more likely to actually be non-adherers, since they have more characteristics that are viewed as indicators of high self-perceived health and low disease awareness, possibly making the subjects less adherent to study medication. We suggest that in pharmacogenetic research, extreme non-responders should be excluded to overcome the problem that non-adherence is investigated instead of non-responsiveness.
authors.affiliation: Department of Cardiology, C5-R, Leiden University Medical Center, PO Box 9600, 2300 RC, Leiden, The Netherlands. s.trompet@lumc.nl.|Department of Gerontology and Geriatrics, Leiden University Medical Center, Leiden, The Netherlands. s.trompet@lumc.nl.
authors.forename: S
authors.initials: S
authors.lastname: Trompet
authors.affiliation: Department of Gerontology and Geriatrics, Leiden University Medical Center, Leiden, The Netherlands.
authors.forename: I
authors.initials: I
authors.lastname: Postmus
authors.affiliation: Section of Molecular Epidemiology, Leiden University Medical Center, Leiden, The Netherlands.
authors.forename: P E
authors.initials: PE
authors.lastname: Slagboom
authors.affiliation: Section of Molecular Epidemiology, Leiden University Medical Center, Leiden, The Netherlands.
authors.forename: B T
authors.initials: BT
authors.lastname: Heijmans
authors.affiliation: Department of Cardiology, C5-R, Leiden University Medical Center, PO Box 9600, 2300 RC, Leiden, The Netherlands.|Department of Gerontology and Geriatrics, Leiden University Medical Center, Leiden, The Netherlands.
authors.forename: R A J
authors.initials: RA
authors.lastname: Smit
authors.affiliation: Section Gerontology and Geriatrics, Department of Internal Medicine, VU Medical Center, Amsterdam, The Netherlands.
authors.forename: A B
authors.initials: AB
authors.lastname: Maier
authors.affiliation: Department of Pharmacology and Therapeutics, University College Cork, Cork, Ireland.
authors.forename: B M
authors.initials: BM
authors.lastname: Buckley
authors.affiliation: BHF Glasgow Cardiovascular Research Centre, Faculty of Medicine, Glasgow, UK.
authors.forename: N
authors.initials: N
authors.lastname: Sattar
authors.affiliation: Institute of Cardiovascular and Medical Sciences, Faculty of Medicine, University of Glasgow, Glasgow, UK.
authors.forename: D J
authors.initials: DJ
authors.lastname: Stott
authors.affiliation: Robertson Center for Biostatistics, University of Glasgow, Glasgow, UK.
authors.forename: I
authors.initials: I
authors.lastname: Ford
authors.affiliation: Faculty of Health and Medical Sciences, Department of Public Health, University of Copenhagen, Copenhagen, Denmark.
authors.forename: R G J
authors.initials: RG
authors.lastname: Westendorp
authors.affiliation: Department of Gerontology and Geriatrics, Leiden University Medical Center, Leiden, The Netherlands.
authors.forename: A J M
authors.initials: AJ
authors.lastname: de Craen
authors.affiliation: Department of Cardiology, C5-R, Leiden University Medical Center, PO Box 9600, 2300 RC, Leiden, The Netherlands.|Durrer Center for Cardiogenetic Research, Amsterdam, The Netherlands.|Interuniversity Cardiology Institute of the Netherlands, Utrecht, the Netherlands.
authors.forename: J W
authors.initials: JW
authors.lastname: Jukema
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D008078:Cholesterol, LDL / Q000097:blood; D005260:Female; D014644:Genetic Variation / Q000235:genetics; D006801:Humans; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000627:therapeutic use*; D008297:Male; D010597:Pharmacogenetics / Q000379:methods; D000071185:Pharmacogenomic Testing; D017035:Pravastatin / Q000627:therapeutic use; D011446:Prospective Studies; D016032:Randomized Controlled Trials as Topic; D012306:Risk; D016896:Treatment Outcome
chemical_list: D008078:Cholesterol, LDL; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D017035:Pravastatin
keywords: Adherence; Cardiovascular; Pharmacogenetics; Statins