Non-response to (statin) therapy: The importance of distinguishing non-responders from non-adherers in pharmacogenetic studies
Trompet, S.; Postmus, I.; Slagboom, P. E.; Heijmans, B. T.; Smit, R. A. J.; Maier, A. B.; Buckley, Brendan M.; Sattar, N.; Stott, D. J.; Ford, I.; Westendorp, R. G. J.; de Craen, A. J. M.; Jukema, J. W.
Date:
2015-12-19
Copyright:
©The Author(s) 2015. This article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made.
Citation:
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. (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
Abstract:
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.
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Except where otherwise noted, this item's license is described as ©The Author(s) 2015. This article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made.