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

S. Trompet, I. Postmus, E.P. Slagboom, B.T. Heijmans, R. A J Smit, A. B. Maier, B.M. Buckley, N. Sattar, D.J. Stott, I. Ford, R.G.J. Westendorp, A.J.M. Craen, J.W. Jukema

Research output: Contribution to JournalArticleAcademicpeer-review

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.

Original languageEnglish
Pages (from-to)431-437
Number of pages7
JournalEuropean Journal of Clinical Pharmacology
Volume72
Issue number4
Early online date19 Dec 2015
DOIs
Publication statusPublished - Apr 2016

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Hydroxymethylglutaryl-CoA Reductase Inhibitors
Pharmacogenetics
Pravastatin
Therapeutics
Genetic Loci
Genetic Association Studies
Research
Alcohol Drinking
LDL Cholesterol
Cognition
Linear Models
Regression Analysis
Pharmacogenomic Testing
Prospective Studies
Hypertension
Health

Keywords

  • Adherence
  • Cardiovascular
  • Pharmacogenetics
  • Statins

Cite this

Trompet, S. ; Postmus, I. ; Slagboom, E.P. ; Heijmans, B.T. ; Smit, R. A J ; Maier, A. B. ; Buckley, B.M. ; Sattar, N. ; Stott, D.J. ; Ford, I. ; Westendorp, R.G.J. ; Craen, A.J.M. ; Jukema, J.W. / Non-response to (statin) therapy : The importance of distinguishing non-responders from non-adherers in pharmacogenetic studies. In: European Journal of Clinical Pharmacology. 2016 ; Vol. 72, No. 4. pp. 431-437.
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title = "Non-response to (statin) therapy: The importance of distinguishing non-responders from non-adherers in pharmacogenetic studies",
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",
author = "S. Trompet and I. Postmus and E.P. Slagboom and B.T. Heijmans and Smit, {R. A J} and Maier, {A. B.} and B.M. Buckley and N. Sattar and D.J. Stott and I. Ford and R.G.J. Westendorp and A.J.M. Craen and J.W. Jukema",
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Trompet, S, Postmus, I, Slagboom, EP, Heijmans, BT, Smit, RAJ, Maier, AB, Buckley, BM, Sattar, N, Stott, DJ, Ford, I, Westendorp, RGJ, Craen, AJM & Jukema, JW 2016, 'Non-response to (statin) therapy: The importance of distinguishing non-responders from non-adherers in pharmacogenetic studies' European Journal of Clinical Pharmacology, vol. 72, no. 4, pp. 431-437. https://doi.org/10.1007/s00228-015-1994-9

Non-response to (statin) therapy : The importance of distinguishing non-responders from non-adherers in pharmacogenetic studies. / Trompet, S.; Postmus, I.; Slagboom, E.P.; Heijmans, B.T.; Smit, R. A J; Maier, A. B.; Buckley, B.M.; Sattar, N.; Stott, D.J.; Ford, I.; Westendorp, R.G.J.; Craen, A.J.M.; Jukema, J.W.

In: European Journal of Clinical Pharmacology, Vol. 72, No. 4, 04.2016, p. 431-437.

Research output: Contribution to JournalArticleAcademicpeer-review

TY - JOUR

T1 - Non-response to (statin) therapy

T2 - The importance of distinguishing non-responders from non-adherers in pharmacogenetic studies

AU - Trompet, S.

AU - Postmus, I.

AU - Slagboom, E.P.

AU - Heijmans, B.T.

AU - Smit, R. A J

AU - Maier, A. B.

AU - Buckley, B.M.

AU - Sattar, N.

AU - Stott, D.J.

AU - Ford, I.

AU - Westendorp, R.G.J.

AU - Craen, A.J.M.

AU - Jukema, J.W.

PY - 2016/4

Y1 - 2016/4

N2 - 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.

AB - 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.

KW - Adherence

KW - Cardiovascular

KW - Pharmacogenetics

KW - Statins

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JO - European Journal of Clinical Pharmacology

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