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

S Trompet; I Postmus; P E 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 de Craen; J W Jukema

doi:10.1007/s00228-015-1994-9

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

S Trompet, I Postmus, P E 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 de Craen, J W Jukema

https://www.ifsv.ku.dk/om-instituttet/socialmedicin/

16 Citationer (Scopus)

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.

Originalsprog	Engelsk
Tidsskrift	European Journal of Clinical Pharmacology
Vol/bind	72
Udgave nummer	4
Sider (fra-til)	431–437
Antal sider	7
ISSN	0031-6970
DOI	https://doi.org/10.1007/s00228-015-1994-9
Status	Udgivet - apr. 2016

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10.1007/s00228-015-1994-9Licens: CC BY

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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., & 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), 431–437. https://doi.org/10.1007/s00228-015-1994-9

Trompet, S, Postmus, I, Slagboom, PE, Heijmans, BT, Smit, RAJ, Maier, AB, Buckley, BM, Sattar, N, Stott, DJ, Ford, I, Westendorp, RGJ, de 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, bind 72, nr. 4, s. 431–437. https://doi.org/10.1007/s00228-015-1994-9

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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.",

author = "S Trompet and I Postmus and Slagboom, {P E} and Heijmans, {B T} and Smit, {R A J} and Maier, {A B} and Buckley, {B M} and N Sattar and Stott, {D J} and I Ford and Westendorp, {R G J} and {de Craen}, {A J M} and Jukema, {J W}",

year = "2016",

month = apr,

doi = "10.1007/s00228-015-1994-9",

language = "English",

volume = "72",

pages = "431–437",

journal = "European Journal of Clinical Pharmacology",

issn = "0031-6970",

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number = "4",

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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, P E

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 - de 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.

U2 - 10.1007/s00228-015-1994-9

DO - 10.1007/s00228-015-1994-9

M3 - Journal article

C2 - 26686871

SN - 0031-6970

VL - 72

SP - 431

EP - 437

JO - European Journal of Clinical Pharmacology

JF - European Journal of Clinical Pharmacology

IS - 4

ER -

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

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