Regression of coronary atherosclerosis with infusions of the high-density lipoprotein mimetic CER-001 in patients with more extensive plaque burden

Yu Kataoka, Jordan Andrews, MyNgan Duong, Tracy Nguyen, Nisha Schwarz, Jessica Fendler, Rishi Puri, Julie Butters, Constance Keyserling, John F Paolini, Jean-Louis Dasseux, Stephen J Nicholls

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Abstract

BACKGROUND: CER-001 is an engineered pre-beta high-density lipoprotein (HDL) mimetic, which rapidly mobilizes cholesterol. Infusion of CER-001 3 mg/kg exhibited a potentially favorable effect on plaque burden in the CHI-SQUARE (Can HDL Infusions Significantly Quicken Atherosclerosis Regression) study. Since baseline atheroma burden has been shown as a determinant for the efficacy of HDL infusions, the degree of baseline atheroma burden might influence the effect of CER-001.

METHODS: CHI-SQUARE compared the effect of 6 weekly infusions of CER-001 (3, 6 and 12 mg/kg) vs. placebo on coronary atherosclerosis in 369 patients with acute coronary syndrome (ACS) using serial intravascular ultrasound (IVUS). Baseline percent atheroma volume (B-PAV) cutoff associated with atheroma regression following CER-001 infusions was determined by receiver-operating characteristics curve analysis. 369 subjects were stratified according to the cutoff. The effect of CER-001 at different doses was compared to placebo in each group.

RESULTS: A B-PAV ≥30% was the optimal cutoff associated with PAV regression following CER-001 infusions. CER-001 induced PAV regression in patients with B-PAV ≥30% but not in those with B-PAV <30% (-0.45%±2.65% vs. +0.34%±1.69%, P=0.01). Compared to placebo, the greatest PAV regression was observed with CER-001 3mg/kg in patients with B-PAV ≥30% (-0.96%±0.34% vs. -0.25%±0.31%, P=0.01), whereas there were no differences between placebo (+0.09%±0.36%) versus CER-001 in patients with B-PAV <30% (3 mg/kg; +0.41%±0.32%, P=0.39; 6 mg/kg; +0.27%±0.36%, P=0.76; 12 mg/kg; +0.32%±0.37%, P=0.97).

CONCLUSIONS: Infusions of CER-001 3 mg/kg induced the greatest atheroma regression in ACS patients with higher B-PAV. These findings identify ACS patients with more extensive disease as most likely to benefit from HDL mimetic therapy.

LanguageEnglish
Pages252-263
Number of pages12
JournalCardiovascular Diagnosis and Therapy
Volume7
Issue number3
DOIs
Publication statusPublished - Jun 2017

Keywords

  • Journal Article

Cite this

Kataoka, Yu ; Andrews, Jordan ; Duong, MyNgan ; Nguyen, Tracy ; Schwarz, Nisha ; Fendler, Jessica ; Puri, Rishi ; Butters, Julie ; Keyserling, Constance ; Paolini, John F ; Dasseux, Jean-Louis ; Nicholls, Stephen J. / Regression of coronary atherosclerosis with infusions of the high-density lipoprotein mimetic CER-001 in patients with more extensive plaque burden. In: Cardiovascular Diagnosis and Therapy. 2017 ; Vol. 7, No. 3. pp. 252-263.
@article{488e54e9da43492fb41a0d63eb12efae,
title = "Regression of coronary atherosclerosis with infusions of the high-density lipoprotein mimetic CER-001 in patients with more extensive plaque burden",
abstract = "BACKGROUND: CER-001 is an engineered pre-beta high-density lipoprotein (HDL) mimetic, which rapidly mobilizes cholesterol. Infusion of CER-001 3 mg/kg exhibited a potentially favorable effect on plaque burden in the CHI-SQUARE (Can HDL Infusions Significantly Quicken Atherosclerosis Regression) study. Since baseline atheroma burden has been shown as a determinant for the efficacy of HDL infusions, the degree of baseline atheroma burden might influence the effect of CER-001.METHODS: CHI-SQUARE compared the effect of 6 weekly infusions of CER-001 (3, 6 and 12 mg/kg) vs. placebo on coronary atherosclerosis in 369 patients with acute coronary syndrome (ACS) using serial intravascular ultrasound (IVUS). Baseline percent atheroma volume (B-PAV) cutoff associated with atheroma regression following CER-001 infusions was determined by receiver-operating characteristics curve analysis. 369 subjects were stratified according to the cutoff. The effect of CER-001 at different doses was compared to placebo in each group.RESULTS: A B-PAV ≥30{\%} was the optimal cutoff associated with PAV regression following CER-001 infusions. CER-001 induced PAV regression in patients with B-PAV ≥30{\%} but not in those with B-PAV <30{\%} (-0.45{\%}±2.65{\%} vs. +0.34{\%}±1.69{\%}, P=0.01). Compared to placebo, the greatest PAV regression was observed with CER-001 3mg/kg in patients with B-PAV ≥30{\%} (-0.96{\%}±0.34{\%} vs. -0.25{\%}±0.31{\%}, P=0.01), whereas there were no differences between placebo (+0.09{\%}±0.36{\%}) versus CER-001 in patients with B-PAV <30{\%} (3 mg/kg; +0.41{\%}±0.32{\%}, P=0.39; 6 mg/kg; +0.27{\%}±0.36{\%}, P=0.76; 12 mg/kg; +0.32{\%}±0.37{\%}, P=0.97).CONCLUSIONS: Infusions of CER-001 3 mg/kg induced the greatest atheroma regression in ACS patients with higher B-PAV. These findings identify ACS patients with more extensive disease as most likely to benefit from HDL mimetic therapy.",
keywords = "Journal Article",
author = "Yu Kataoka and Jordan Andrews and MyNgan Duong and Tracy Nguyen and Nisha Schwarz and Jessica Fendler and Rishi Puri and Julie Butters and Constance Keyserling and Paolini, {John F} and Jean-Louis Dasseux and Nicholls, {Stephen J}",
year = "2017",
month = "6",
doi = "10.21037/cdt.2017.02.01",
language = "English",
volume = "7",
pages = "252--263",
journal = "Cardiovascular Diagnosis and Therapy",
issn = "2223-3652",
publisher = "AME Publishing Company",
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Kataoka, Y, Andrews, J, Duong, M, Nguyen, T, Schwarz, N, Fendler, J, Puri, R, Butters, J, Keyserling, C, Paolini, JF, Dasseux, J-L & Nicholls, SJ 2017, 'Regression of coronary atherosclerosis with infusions of the high-density lipoprotein mimetic CER-001 in patients with more extensive plaque burden', Cardiovascular Diagnosis and Therapy, vol. 7, no. 3, pp. 252-263. https://doi.org/10.21037/cdt.2017.02.01

Regression of coronary atherosclerosis with infusions of the high-density lipoprotein mimetic CER-001 in patients with more extensive plaque burden. / Kataoka, Yu; Andrews, Jordan; Duong, MyNgan; Nguyen, Tracy; Schwarz, Nisha; Fendler, Jessica; Puri, Rishi; Butters, Julie; Keyserling, Constance; Paolini, John F; Dasseux, Jean-Louis; Nicholls, Stephen J.

In: Cardiovascular Diagnosis and Therapy, Vol. 7, No. 3, 06.2017, p. 252-263.

Research output: Contribution to journalArticle

TY - JOUR

T1 - Regression of coronary atherosclerosis with infusions of the high-density lipoprotein mimetic CER-001 in patients with more extensive plaque burden

AU - Kataoka, Yu

AU - Andrews, Jordan

AU - Duong, MyNgan

AU - Nguyen, Tracy

AU - Schwarz, Nisha

AU - Fendler, Jessica

AU - Puri, Rishi

AU - Butters, Julie

AU - Keyserling, Constance

AU - Paolini, John F

AU - Dasseux, Jean-Louis

AU - Nicholls, Stephen J

PY - 2017/6

Y1 - 2017/6

N2 - BACKGROUND: CER-001 is an engineered pre-beta high-density lipoprotein (HDL) mimetic, which rapidly mobilizes cholesterol. Infusion of CER-001 3 mg/kg exhibited a potentially favorable effect on plaque burden in the CHI-SQUARE (Can HDL Infusions Significantly Quicken Atherosclerosis Regression) study. Since baseline atheroma burden has been shown as a determinant for the efficacy of HDL infusions, the degree of baseline atheroma burden might influence the effect of CER-001.METHODS: CHI-SQUARE compared the effect of 6 weekly infusions of CER-001 (3, 6 and 12 mg/kg) vs. placebo on coronary atherosclerosis in 369 patients with acute coronary syndrome (ACS) using serial intravascular ultrasound (IVUS). Baseline percent atheroma volume (B-PAV) cutoff associated with atheroma regression following CER-001 infusions was determined by receiver-operating characteristics curve analysis. 369 subjects were stratified according to the cutoff. The effect of CER-001 at different doses was compared to placebo in each group.RESULTS: A B-PAV ≥30% was the optimal cutoff associated with PAV regression following CER-001 infusions. CER-001 induced PAV regression in patients with B-PAV ≥30% but not in those with B-PAV <30% (-0.45%±2.65% vs. +0.34%±1.69%, P=0.01). Compared to placebo, the greatest PAV regression was observed with CER-001 3mg/kg in patients with B-PAV ≥30% (-0.96%±0.34% vs. -0.25%±0.31%, P=0.01), whereas there were no differences between placebo (+0.09%±0.36%) versus CER-001 in patients with B-PAV <30% (3 mg/kg; +0.41%±0.32%, P=0.39; 6 mg/kg; +0.27%±0.36%, P=0.76; 12 mg/kg; +0.32%±0.37%, P=0.97).CONCLUSIONS: Infusions of CER-001 3 mg/kg induced the greatest atheroma regression in ACS patients with higher B-PAV. These findings identify ACS patients with more extensive disease as most likely to benefit from HDL mimetic therapy.

AB - BACKGROUND: CER-001 is an engineered pre-beta high-density lipoprotein (HDL) mimetic, which rapidly mobilizes cholesterol. Infusion of CER-001 3 mg/kg exhibited a potentially favorable effect on plaque burden in the CHI-SQUARE (Can HDL Infusions Significantly Quicken Atherosclerosis Regression) study. Since baseline atheroma burden has been shown as a determinant for the efficacy of HDL infusions, the degree of baseline atheroma burden might influence the effect of CER-001.METHODS: CHI-SQUARE compared the effect of 6 weekly infusions of CER-001 (3, 6 and 12 mg/kg) vs. placebo on coronary atherosclerosis in 369 patients with acute coronary syndrome (ACS) using serial intravascular ultrasound (IVUS). Baseline percent atheroma volume (B-PAV) cutoff associated with atheroma regression following CER-001 infusions was determined by receiver-operating characteristics curve analysis. 369 subjects were stratified according to the cutoff. The effect of CER-001 at different doses was compared to placebo in each group.RESULTS: A B-PAV ≥30% was the optimal cutoff associated with PAV regression following CER-001 infusions. CER-001 induced PAV regression in patients with B-PAV ≥30% but not in those with B-PAV <30% (-0.45%±2.65% vs. +0.34%±1.69%, P=0.01). Compared to placebo, the greatest PAV regression was observed with CER-001 3mg/kg in patients with B-PAV ≥30% (-0.96%±0.34% vs. -0.25%±0.31%, P=0.01), whereas there were no differences between placebo (+0.09%±0.36%) versus CER-001 in patients with B-PAV <30% (3 mg/kg; +0.41%±0.32%, P=0.39; 6 mg/kg; +0.27%±0.36%, P=0.76; 12 mg/kg; +0.32%±0.37%, P=0.97).CONCLUSIONS: Infusions of CER-001 3 mg/kg induced the greatest atheroma regression in ACS patients with higher B-PAV. These findings identify ACS patients with more extensive disease as most likely to benefit from HDL mimetic therapy.

KW - Journal Article

U2 - 10.21037/cdt.2017.02.01

DO - 10.21037/cdt.2017.02.01

M3 - Article

VL - 7

SP - 252

EP - 263

JO - Cardiovascular Diagnosis and Therapy

T2 - Cardiovascular Diagnosis and Therapy

JF - Cardiovascular Diagnosis and Therapy

SN - 2223-3652

IS - 3

ER -