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

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dc.contributor.authorTrompet, S.
dc.contributor.authorPostmus, I.
dc.contributor.authorSlagboom, P. E.
dc.contributor.authorHeijmans, B. T.
dc.contributor.authorSmit, R. A. J.
dc.contributor.authorMaier, A. B.
dc.contributor.authorBuckley, Brendan M.
dc.contributor.authorSattar, N.
dc.contributor.authorStott, D. J.
dc.contributor.authorFord, I.
dc.contributor.authorWestendorp, R. G. J.
dc.contributor.authorde Craen, A. J. M.
dc.contributor.authorJukema, J. W.
dc.contributor.funderSixth Framework Programmeen
dc.date.accessioned2019-10-26T07:04:22Z
dc.date.available2019-10-26T07:04:22Z
dc.date.issued2015-12-19
dc.description.abstractPurpose: 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.en
dc.description.sponsorshipEuropean Union’s Seventh Framework Programme (FP7/2007-2013) (Grant agreement no. HEALTH-F2-2009-223004)en
dc.description.statusPeer revieweden
dc.description.versionPublished Versionen
dc.format.mimetypeapplication/pdfen
dc.identifier.citationTrompet, 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/s00228-015-1994-9en
dc.identifier.doi10.1007/s00228-015-1994-9en
dc.identifier.eissn1432-1041
dc.identifier.endpage437en
dc.identifier.issn0031-6970
dc.identifier.issued4en
dc.identifier.journaltitleEuropean Journal of Clinical Pharmacologyen
dc.identifier.startpage431en
dc.identifier.urihttps://hdl.handle.net/10468/8879
dc.identifier.volume72en
dc.language.isoenen
dc.publisherSpringer Berlin Heidelbergen
dc.relation.urihttps://link.springer.com/article/10.1007%2Fs00228-015-1994-9
dc.rights©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.en
dc.rights.urihttp://creativecommons.org/licenses/by/4.0/en
dc.subjectPharmacogeneticsen
dc.subjectAdherenceen
dc.subjectStatinsen
dc.subjectCardiovascularen
dc.titleNon-response to (statin) therapy: The importance of distinguishing non-responders from non-adherers in pharmacogenetic studiesen
dc.typeArticle (peer-reviewed)en
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