TY - JOUR

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

T2 - An application to the PROSPER randomised 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 W

AU - Westendorp, R G J

N1 - © 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: journals.permissions@oup.com.

PY - 2023

Y1 - 2023

N2 - BACKGROUND & AIMS: Clinical guidelines often recommend to treat 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: We reanalysed the PROSPER randomised 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 to 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).RESULTS: We found an absolute difference in primary outcome events composed of coronary death, non-fatal myocardial infarction, 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.CONCLUSIONS: 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.

AB - BACKGROUND & AIMS: Clinical guidelines often recommend to treat 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: We reanalysed the PROSPER randomised 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 to 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).RESULTS: We found an absolute difference in primary outcome events composed of coronary death, non-fatal myocardial infarction, 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.CONCLUSIONS: 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.

U2 - 10.1093/eurjpc/zwad383

DO - 10.1093/eurjpc/zwad383

M3 - Journal article

C2 - 38085032

JO - European Journal of Preventive Cardiology

JF - European Journal of Preventive Cardiology

SN - 2047-4873

ER -