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

Trompet, S. et al. (2016) Non-response to (statin) therapy: the importance of distinguishing non-responders from non-adherers in pharmacogenetic studies. European Journal of Clinical Pharmacology, 72(4), pp. 431-437. (doi: 10.1007/s00228-015-1994-9) (PMID:26686871)

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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.

Item Type:Articles
Additional Information:Funded from the European Union’s Seventh Framework Programme (FP7/2007-2013) under grant agreement no. HEALTH-F2-2009- 223004. This work was performed as part of an ongoing collaboration of the PROSPER study group in the universities of Leiden, Glasgow, and Cork.
Glasgow Author(s) Enlighten ID:Stott J, Professor David and Ford, Professor Ian and Sattar, Professor Naveed
Authors: Trompet, S., Postmus, I., Slagboom, P.E., Heijmans, B.T., Smit, R.A.J., Maier, A.B., Buckley, B.M., Sattar, N., Stott, D.J., Ford, I., Westendorp, R.G.J., de Craen, A.J.M., and Jukema, J.W.
College/School:College of Medical Veterinary and Life Sciences > School of Cardiovascular & Metabolic Health
College of Medical Veterinary and Life Sciences > School of Health & Wellbeing > Robertson Centre
Journal Name:European Journal of Clinical Pharmacology
ISSN (Online):1432-1041
Copyright Holders:Copyright © 2015 The Authors
First Published:First published in European Journal of Clinical Pharmacology 72:431-437
Publisher Policy:Reproduced under a Creative Commons License

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