The potential benefit of statin prescription based on prediction of treatment responsiveness in older individuals: an application to the PROSPER randomized controlled trial

T L Nguyen; S Trompet; J B Brodersen; J Hoogland; T P A Debray; N Sattar; J. Wouter Jukema; Rudi Gerardus Johannes Westendorp

doi:10.1093/eurjpc/zwad383

The potential benefit of statin prescription based on prediction of treatment responsiveness in older individuals: an application to the PROSPER randomized controlled trial

T L Nguyen^*
, S Trompet
, J B Brodersen
, J Hoogland
, T P A Debray
, N Sattar
, J. Wouter Jukema
, Rudi Gerardus Johannes Westendorp

^*Corresponding author for this work

Primary Health Care

Research output: Contribution to journal › Article › Research › peer-review

Abstract

AIMS: Clinical guidelines often recommend treating individuals based on their cardiovascular risk. We revisit this paradigm and quantify the efficacy of three treatment strategies: (i) overall prescription, i.e. treatment to all individuals sharing the eligibility criteria of a trial; (ii) risk-stratified prescription, i.e. treatment only to those at an elevated outcome risk; and (iii) prescription based on predicted treatment responsiveness.

METHODS AND RESULTS: We reanalysed the PROSPER randomized controlled trial, which included individuals aged 70-82 years with a history of, or risk factors for, vascular diseases. We conducted the derivation and internal-external validation of a model predicting treatment responsiveness. We compared with placebo (n = 2913): (i) pravastatin (n = 2891); (ii) pravastatin in the presence of previous vascular diseases and placebo in the absence thereof (n = 2925); and (iii) pravastatin in the presence of a favourable prediction of treatment response and placebo in the absence thereof (n = 2890). We found an absolute difference in primary outcome events composed of coronary death, non-fatal myocardial infarction, and fatal or non-fatal stroke, per 10 000 person-years equal to: -78 events (95% CI, -144 to -12) when prescribing pravastatin to all participants; -66 events (95% CI, -114 to -18) when treating only individuals with an elevated vascular risk; and -103 events (95% CI, -162 to -44) when restricting pravastatin to individuals with a favourable prediction of treatment response.

CONCLUSION: Pravastatin prescription based on predicted responsiveness may have an encouraging potential for cardiovascular prevention. Further external validation of our results and clinical experiments are needed.

TRIAL REGISTRATION: ISRCTN40976937.

Original language	English
Pages (from-to)	945-953
Number of pages	9
Journal	European Journal of Preventive Cardiology
Volume	31
Issue number	8
Early online date	12 Dec 2023
DOIs	https://doi.org/10.1093/eurjpc/zwad383
Publication status	Published - 3 Jun 2024

Funding

T.L.N. expresses his gratitude to Dr A. Rieckmann, Prof N.H. Rod, and Prof T. Lange for their initial input at the conceptualization stage of this research. J.H. acknowledges financial support from the Netherlands Organisation for Health Research and Development (grant 91215058). T.P.A.D. is supported by a project that received funding from the European Union's Horizon 2020 research and innovation programme under ReCoDID grant agreement no. 825746. N.S. is supported by British Heart Foundation Centre of Research Excellence grant RE/18/6/34217. R.G.J.W. is supported by a research grant of Novo Nordisk Fonden: 'Harnessing the Power of Big Data to Address the Societal Challenge of Aging [NNF17OC0027812]'.

Funders	Funder number
University of Copenhagen	91215058
Netherlands Organisation for Health Research and Development	825746
European Union	RE/18/6/34217
British Heart Foundation	NNF17OC0027812
Novo Nordisk Foundation

Keywords

Age Factors
Aged
Aged, 80 and over
Cardiovascular Diseases/prevention & control
Decision Support Techniques
Drug Prescriptions
Female
Heart Disease Risk Factors
Humans
Hydroxymethylglutaryl-CoA Reductase Inhibitors/therapeutic use
Male
Pravastatin/therapeutic use
Risk Assessment
Time Factors
Treatment Outcome
Prediction
Cardiovascular prevention
Statin
Individualized treatment effect

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10.1093/eurjpc/zwad383

Cite this

Nguyen, T. L., Trompet, S., Brodersen, J. B., Hoogland, J., Debray, T. P. A., Sattar, N., Jukema, J. W., & Westendorp, R. G. J. (2024). The potential benefit of statin prescription based on prediction of treatment responsiveness in older individuals: an application to the PROSPER randomized controlled trial. European Journal of Preventive Cardiology, 31(8), 945-953. https://doi.org/10.1093/eurjpc/zwad383

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title = "The potential benefit of statin prescription based on prediction of treatment responsiveness in older individuals: an application to the PROSPER randomized controlled trial",

abstract = "AIMS: Clinical guidelines often recommend treating individuals based on their cardiovascular risk. We revisit this paradigm and quantify the efficacy of three treatment strategies: (i) overall prescription, i.e. treatment to all individuals sharing the eligibility criteria of a trial; (ii) risk-stratified prescription, i.e. treatment only to those at an elevated outcome risk; and (iii) prescription based on predicted treatment responsiveness.METHODS AND RESULTS: We reanalysed the PROSPER randomized controlled trial, which included individuals aged 70-82 years with a history of, or risk factors for, vascular diseases. We conducted the derivation and internal-external validation of a model predicting treatment responsiveness. We compared with placebo (n = 2913): (i) pravastatin (n = 2891); (ii) pravastatin in the presence of previous vascular diseases and placebo in the absence thereof (n = 2925); and (iii) pravastatin in the presence of a favourable prediction of treatment response and placebo in the absence thereof (n = 2890). We found an absolute difference in primary outcome events composed of coronary death, non-fatal myocardial infarction, and fatal or non-fatal stroke, per 10 000 person-years equal to: -78 events (95\% CI, -144 to -12) when prescribing pravastatin to all participants; -66 events (95\% CI, -114 to -18) when treating only individuals with an elevated vascular risk; and -103 events (95\% CI, -162 to -44) when restricting pravastatin to individuals with a favourable prediction of treatment response.CONCLUSION: Pravastatin prescription based on predicted responsiveness may have an encouraging potential for cardiovascular prevention. Further external validation of our results and clinical experiments are needed.TRIAL REGISTRATION: ISRCTN40976937.",

keywords = "Age Factors, Aged, Aged, 80 and over, Cardiovascular Diseases/prevention \& control, Decision Support Techniques, Drug Prescriptions, Female, Heart Disease Risk Factors, Humans, Hydroxymethylglutaryl-CoA Reductase Inhibitors/therapeutic use, Male, Pravastatin/therapeutic use, Risk Assessment, Time Factors, Treatment Outcome, Prediction, Cardiovascular prevention, Statin, Individualized treatment effect",

author = "Nguyen, \{T L\} and S Trompet and Brodersen, \{J B\} and J Hoogland and Debray, \{T P A\} and N Sattar and Jukema, \{J. Wouter\} and Westendorp, \{Rudi Gerardus Johannes\}",

note = "{\textcopyright} The Author(s) 2023. Published by Oxford University Press on behalf of the European Society of Cardiology. All rights reserved. For permissions, please e-mail: [email protected].",

year = "2024",

month = jun,

day = "3",

doi = "10.1093/eurjpc/zwad383",

language = "English",

volume = "31",

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publisher = "Oxford University Press",

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Nguyen, TL, Trompet, S, Brodersen, JB, Hoogland, J, Debray, TPA, Sattar, N, Jukema, JW & Westendorp, RGJ 2024, 'The potential benefit of statin prescription based on prediction of treatment responsiveness in older individuals: an application to the PROSPER randomized controlled trial', European Journal of Preventive Cardiology, vol. 31, no. 8, pp. 945-953. https://doi.org/10.1093/eurjpc/zwad383

The potential benefit of statin prescription based on prediction of treatment responsiveness in older individuals: an application to the PROSPER randomized controlled trial. / Nguyen, T L; Trompet, S; Brodersen, J B et al.
In: European Journal of Preventive Cardiology, Vol. 31, No. 8, 03.06.2024, p. 945-953.

Research output: Contribution to journal › Article › Research › peer-review

TY - JOUR

T1 - The potential benefit of statin prescription based on prediction of treatment responsiveness in older individuals

T2 - an application to the PROSPER randomized controlled trial

AU - Nguyen, T L

AU - Trompet, S

AU - Brodersen, J B

AU - Hoogland, J

AU - Debray, T P A

AU - Sattar, N

AU - Jukema, J. Wouter

AU - Westendorp, Rudi Gerardus Johannes

PY - 2024/6/3

Y1 - 2024/6/3

N2 - AIMS: Clinical guidelines often recommend treating individuals based on their cardiovascular risk. We revisit this paradigm and quantify the efficacy of three treatment strategies: (i) overall prescription, i.e. treatment to all individuals sharing the eligibility criteria of a trial; (ii) risk-stratified prescription, i.e. treatment only to those at an elevated outcome risk; and (iii) prescription based on predicted treatment responsiveness.METHODS AND RESULTS: We reanalysed the PROSPER randomized controlled trial, which included individuals aged 70-82 years with a history of, or risk factors for, vascular diseases. We conducted the derivation and internal-external validation of a model predicting treatment responsiveness. We compared with placebo (n = 2913): (i) pravastatin (n = 2891); (ii) pravastatin in the presence of previous vascular diseases and placebo in the absence thereof (n = 2925); and (iii) pravastatin in the presence of a favourable prediction of treatment response and placebo in the absence thereof (n = 2890). We found an absolute difference in primary outcome events composed of coronary death, non-fatal myocardial infarction, and fatal or non-fatal stroke, per 10 000 person-years equal to: -78 events (95% CI, -144 to -12) when prescribing pravastatin to all participants; -66 events (95% CI, -114 to -18) when treating only individuals with an elevated vascular risk; and -103 events (95% CI, -162 to -44) when restricting pravastatin to individuals with a favourable prediction of treatment response.CONCLUSION: Pravastatin prescription based on predicted responsiveness may have an encouraging potential for cardiovascular prevention. Further external validation of our results and clinical experiments are needed.TRIAL REGISTRATION: ISRCTN40976937.

AB - AIMS: Clinical guidelines often recommend treating individuals based on their cardiovascular risk. We revisit this paradigm and quantify the efficacy of three treatment strategies: (i) overall prescription, i.e. treatment to all individuals sharing the eligibility criteria of a trial; (ii) risk-stratified prescription, i.e. treatment only to those at an elevated outcome risk; and (iii) prescription based on predicted treatment responsiveness.METHODS AND RESULTS: We reanalysed the PROSPER randomized controlled trial, which included individuals aged 70-82 years with a history of, or risk factors for, vascular diseases. We conducted the derivation and internal-external validation of a model predicting treatment responsiveness. We compared with placebo (n = 2913): (i) pravastatin (n = 2891); (ii) pravastatin in the presence of previous vascular diseases and placebo in the absence thereof (n = 2925); and (iii) pravastatin in the presence of a favourable prediction of treatment response and placebo in the absence thereof (n = 2890). We found an absolute difference in primary outcome events composed of coronary death, non-fatal myocardial infarction, and fatal or non-fatal stroke, per 10 000 person-years equal to: -78 events (95% CI, -144 to -12) when prescribing pravastatin to all participants; -66 events (95% CI, -114 to -18) when treating only individuals with an elevated vascular risk; and -103 events (95% CI, -162 to -44) when restricting pravastatin to individuals with a favourable prediction of treatment response.CONCLUSION: Pravastatin prescription based on predicted responsiveness may have an encouraging potential for cardiovascular prevention. Further external validation of our results and clinical experiments are needed.TRIAL REGISTRATION: ISRCTN40976937.

KW - Age Factors

KW - Aged

KW - Aged, 80 and over

KW - Cardiovascular Diseases/prevention & control

KW - Decision Support Techniques

KW - Drug Prescriptions

KW - Female

KW - Heart Disease Risk Factors

KW - Humans

KW - Hydroxymethylglutaryl-CoA Reductase Inhibitors/therapeutic use

KW - Male

KW - Pravastatin/therapeutic use

KW - Risk Assessment

KW - Time Factors

KW - Treatment Outcome

KW - Prediction

KW - Cardiovascular prevention

KW - Statin

KW - Individualized treatment effect

U2 - 10.1093/eurjpc/zwad383

DO - 10.1093/eurjpc/zwad383

M3 - Article

C2 - 38085032

SN - 2047-4873

VL - 31

SP - 945

EP - 953

JO - European Journal of Preventive Cardiology

JF - European Journal of Preventive Cardiology

IS - 8

ER -

The potential benefit of statin prescription based on prediction of treatment responsiveness in older individuals: an application to the PROSPER randomized controlled trial

Abstract

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Keywords

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