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. 2016 Apr;72(4):431-7.
doi: 10.1007/s00228-015-1994-9. Epub 2015 Dec 19.

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

S Trompet  1   2 , I Postmus  3 , P E Slagboom  4 , B T Heijmans  4 , R A J Smit  5   3 , A B Maier  6 , B M Buckley  7 , N Sattar  8 , D J Stott  9 , I Ford  10 , R G J Westendorp  11 , A J M de Craen  3 , J W Jukema  5   12   13
Affiliations

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

S Trompet et al. Eur J Clin Pharmacol. 2016 Apr.

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.

Keywords: Adherence; Cardiovascular; Pharmacogenetics; Statins.

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References

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