Non-response to (statin) therapy: The importance of distinguishing non-responders from non-adherers in pharmacogenetic studies

S. Trompet*, I. Postmus, E.P. Slagboom, B.T. Heijmans, R. A J Smit, A. B. Maier, B.M. Buckley, N. Sattar, D.J. Stott, I. Ford, R.G.J. Westendorp, A.J.M. Craen, J.W. Jukema

*Corresponding author for this work

Research output: Contribution to JournalArticleAcademicpeer-review


PURPOSE: 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.

CONCLUSION: 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.

Original languageEnglish
Pages (from-to)431-437
Number of pages7
JournalEuropean Journal of Clinical Pharmacology
Issue number4
Early online date19 Dec 2015
Publication statusPublished - Apr 2016


  • Adherence
  • Cardiovascular
  • Pharmacogenetics
  • Statins


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