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

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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.
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Springer Berlin Heidelberg
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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.
Pharmacogenetics , Adherence , Statins , Cardiovascular
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