Estimated individual lifetime benefit from PCSK9 inhibition in statin-treated patients with coronary artery disease

Lotte Kaasenbrood, Kausik K. Ray, S. Matthijs Boekholdt, Yvo M. Smulders, John C. LaRosa, John J. P. Kastelein, Yolanda van der Graaf, Johannes A. N. Dorresteijn, Frank L. J. Visseren

Research output: Contribution to journalArticleAcademicpeer-review

Abstract

Objective In statin-treated patients with stable coronary artery disease (CAD), residual risk of cardiovascular events is partly explained by plasma levels of low-density lipoprotein cholesterol (LDL-C). This study aimed to estimate individual benefit of proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibition in CAD patients already treated with high-dose statin. Methods Individual lifetime benefit was estimated in months gain free of stroke or myocardial infarction (MI) until age 80 years. Predictions were based on two competing risk models developed in data from 4853 patients with CAD originating from the atorvastatin 80 mg arm of the Treating to New Targets (TNT) trial. The relative effect of PCSK9 inhibition was added to the models and was assumed based on average estimates from large clinical trials. We accounted for individual LDL-C levels, assuming 50% LDL-C reduction by PCSK9 inhibition and 21% cardiovascular risk reduction per mmol/L (39 mg/dL) LDL-C lowering. Results Estimated individual gain was <6 months in 61% of the patients, 6-12 months in 28% of the patients and ≥12 months in 10% of the patients (median 5, quartiles 2-8 months). Highest estimated benefit was observed in younger patients (aged 40-60 years) with high risk factor burden, particularly if LDL-C levels were >1.8 mmol/L (>70 mg/dL). Estimated benefit was lowest (≤5 months) in older patients (≥70 years), in particular if LDL-C and other risk factors levels were low. Conclusion The individual estimated lifetime benefit from PCSK9 inhibition in patients with stable CAD on high-dose statin varied from <6 to ≥12 months free of stroke or MI. Highest benefit is expected in younger patients (age 40-60 years) with high risk factor burden and relatively high LDL-C levels.
Original languageEnglish
Pages (from-to)1699-1705
JournalHeart
Volume104
Issue number20
DOIs
Publication statusPublished - 2018

Cite this

Kaasenbrood, L., Ray, K. K., Boekholdt, S. M., Smulders, Y. M., LaRosa, J. C., Kastelein, J. J. P., ... Visseren, F. L. J. (2018). Estimated individual lifetime benefit from PCSK9 inhibition in statin-treated patients with coronary artery disease. Heart, 104(20), 1699-1705. https://doi.org/10.1136/heartjnl-2017-312510
Kaasenbrood, Lotte ; Ray, Kausik K. ; Boekholdt, S. Matthijs ; Smulders, Yvo M. ; LaRosa, John C. ; Kastelein, John J. P. ; van der Graaf, Yolanda ; Dorresteijn, Johannes A. N. ; Visseren, Frank L. J. / Estimated individual lifetime benefit from PCSK9 inhibition in statin-treated patients with coronary artery disease. In: Heart. 2018 ; Vol. 104, No. 20. pp. 1699-1705.
@article{ca05069e88ff473c87776c894b6ffaaf,
title = "Estimated individual lifetime benefit from PCSK9 inhibition in statin-treated patients with coronary artery disease",
abstract = "Objective In statin-treated patients with stable coronary artery disease (CAD), residual risk of cardiovascular events is partly explained by plasma levels of low-density lipoprotein cholesterol (LDL-C). This study aimed to estimate individual benefit of proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibition in CAD patients already treated with high-dose statin. Methods Individual lifetime benefit was estimated in months gain free of stroke or myocardial infarction (MI) until age 80 years. Predictions were based on two competing risk models developed in data from 4853 patients with CAD originating from the atorvastatin 80 mg arm of the Treating to New Targets (TNT) trial. The relative effect of PCSK9 inhibition was added to the models and was assumed based on average estimates from large clinical trials. We accounted for individual LDL-C levels, assuming 50{\%} LDL-C reduction by PCSK9 inhibition and 21{\%} cardiovascular risk reduction per mmol/L (39 mg/dL) LDL-C lowering. Results Estimated individual gain was <6 months in 61{\%} of the patients, 6-12 months in 28{\%} of the patients and ≥12 months in 10{\%} of the patients (median 5, quartiles 2-8 months). Highest estimated benefit was observed in younger patients (aged 40-60 years) with high risk factor burden, particularly if LDL-C levels were >1.8 mmol/L (>70 mg/dL). Estimated benefit was lowest (≤5 months) in older patients (≥70 years), in particular if LDL-C and other risk factors levels were low. Conclusion The individual estimated lifetime benefit from PCSK9 inhibition in patients with stable CAD on high-dose statin varied from <6 to ≥12 months free of stroke or MI. Highest benefit is expected in younger patients (age 40-60 years) with high risk factor burden and relatively high LDL-C levels.",
author = "Lotte Kaasenbrood and Ray, {Kausik K.} and Boekholdt, {S. Matthijs} and Smulders, {Yvo M.} and LaRosa, {John C.} and Kastelein, {John J. P.} and {van der Graaf}, Yolanda and Dorresteijn, {Johannes A. N.} and Visseren, {Frank L. J.}",
year = "2018",
doi = "10.1136/heartjnl-2017-312510",
language = "English",
volume = "104",
pages = "1699--1705",
journal = "Heart",
issn = "1355-6037",
publisher = "BMJ Publishing Group",
number = "20",

}

Kaasenbrood, L, Ray, KK, Boekholdt, SM, Smulders, YM, LaRosa, JC, Kastelein, JJP, van der Graaf, Y, Dorresteijn, JAN & Visseren, FLJ 2018, 'Estimated individual lifetime benefit from PCSK9 inhibition in statin-treated patients with coronary artery disease' Heart, vol. 104, no. 20, pp. 1699-1705. https://doi.org/10.1136/heartjnl-2017-312510

Estimated individual lifetime benefit from PCSK9 inhibition in statin-treated patients with coronary artery disease. / Kaasenbrood, Lotte; Ray, Kausik K.; Boekholdt, S. Matthijs; Smulders, Yvo M.; LaRosa, John C.; Kastelein, John J. P.; van der Graaf, Yolanda; Dorresteijn, Johannes A. N.; Visseren, Frank L. J.

In: Heart, Vol. 104, No. 20, 2018, p. 1699-1705.

Research output: Contribution to journalArticleAcademicpeer-review

TY - JOUR

T1 - Estimated individual lifetime benefit from PCSK9 inhibition in statin-treated patients with coronary artery disease

AU - Kaasenbrood, Lotte

AU - Ray, Kausik K.

AU - Boekholdt, S. Matthijs

AU - Smulders, Yvo M.

AU - LaRosa, John C.

AU - Kastelein, John J. P.

AU - van der Graaf, Yolanda

AU - Dorresteijn, Johannes A. N.

AU - Visseren, Frank L. J.

PY - 2018

Y1 - 2018

N2 - Objective In statin-treated patients with stable coronary artery disease (CAD), residual risk of cardiovascular events is partly explained by plasma levels of low-density lipoprotein cholesterol (LDL-C). This study aimed to estimate individual benefit of proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibition in CAD patients already treated with high-dose statin. Methods Individual lifetime benefit was estimated in months gain free of stroke or myocardial infarction (MI) until age 80 years. Predictions were based on two competing risk models developed in data from 4853 patients with CAD originating from the atorvastatin 80 mg arm of the Treating to New Targets (TNT) trial. The relative effect of PCSK9 inhibition was added to the models and was assumed based on average estimates from large clinical trials. We accounted for individual LDL-C levels, assuming 50% LDL-C reduction by PCSK9 inhibition and 21% cardiovascular risk reduction per mmol/L (39 mg/dL) LDL-C lowering. Results Estimated individual gain was <6 months in 61% of the patients, 6-12 months in 28% of the patients and ≥12 months in 10% of the patients (median 5, quartiles 2-8 months). Highest estimated benefit was observed in younger patients (aged 40-60 years) with high risk factor burden, particularly if LDL-C levels were >1.8 mmol/L (>70 mg/dL). Estimated benefit was lowest (≤5 months) in older patients (≥70 years), in particular if LDL-C and other risk factors levels were low. Conclusion The individual estimated lifetime benefit from PCSK9 inhibition in patients with stable CAD on high-dose statin varied from <6 to ≥12 months free of stroke or MI. Highest benefit is expected in younger patients (age 40-60 years) with high risk factor burden and relatively high LDL-C levels.

AB - Objective In statin-treated patients with stable coronary artery disease (CAD), residual risk of cardiovascular events is partly explained by plasma levels of low-density lipoprotein cholesterol (LDL-C). This study aimed to estimate individual benefit of proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibition in CAD patients already treated with high-dose statin. Methods Individual lifetime benefit was estimated in months gain free of stroke or myocardial infarction (MI) until age 80 years. Predictions were based on two competing risk models developed in data from 4853 patients with CAD originating from the atorvastatin 80 mg arm of the Treating to New Targets (TNT) trial. The relative effect of PCSK9 inhibition was added to the models and was assumed based on average estimates from large clinical trials. We accounted for individual LDL-C levels, assuming 50% LDL-C reduction by PCSK9 inhibition and 21% cardiovascular risk reduction per mmol/L (39 mg/dL) LDL-C lowering. Results Estimated individual gain was <6 months in 61% of the patients, 6-12 months in 28% of the patients and ≥12 months in 10% of the patients (median 5, quartiles 2-8 months). Highest estimated benefit was observed in younger patients (aged 40-60 years) with high risk factor burden, particularly if LDL-C levels were >1.8 mmol/L (>70 mg/dL). Estimated benefit was lowest (≤5 months) in older patients (≥70 years), in particular if LDL-C and other risk factors levels were low. Conclusion The individual estimated lifetime benefit from PCSK9 inhibition in patients with stable CAD on high-dose statin varied from <6 to ≥12 months free of stroke or MI. Highest benefit is expected in younger patients (age 40-60 years) with high risk factor burden and relatively high LDL-C levels.

UR - https://www.scopus.com/inward/record.uri?partnerID=HzOxMe3b&scp=85054470858&origin=inward

UR - https://www.ncbi.nlm.nih.gov/pubmed/29622600

U2 - 10.1136/heartjnl-2017-312510

DO - 10.1136/heartjnl-2017-312510

M3 - Article

VL - 104

SP - 1699

EP - 1705

JO - Heart

JF - Heart

SN - 1355-6037

IS - 20

ER -