Long-term darapladib use does not affect coronary plaque composition assessed using multimodality intravascular imaging modalities: A randomized-controlled study

Woong Gil Choi, Megha Prasad, Ryan Lennon, Rajiv Gulati, Abhiram Prasad, Lilach O Lerman, Amir Lerman

Research output: Contribution to journalArticle

1 Citation (Scopus)

Abstract

Background Lipoprotein-associated phospholipase A 2 (Lp-PLA 2) may play a role in plaque progression and vulnerability. We aimed to define plaque characteristics on multimodality intravascular imaging in patients with coronary endothelial dysfunction in response to long-term inhibition of Lp-PLA2 by darapladib. Patients and methods This is a double-blinded, randomized study screening 70 patients, and enrolling 54 patients with suspected ischemia, without obstructive disease on angiography and with coronary endothelial dysfunction by invasive assessment. Patients were randomized to receive darapladib or placebo for 6 months. Forty patients underwent multimodality intravascular imaging at baseline and after 6 months of therapy. Several parameters of plaque vulnerability were measured, including maximum value of lipid core burden index for any of the 4-mm segment (maxLCBI 4 mm) by near-infrared spectroscopy. Microchannels and macrophages were assessed using optical coherence tomography and necrotic core volume by virtual histology intravascular ultrasound. Results There was no significant difference in maxLCBI 4 mm [64.56 (7.74, 128.56) vs. 22.43 (0, 75.63), P=0.522] or in macrophage images angle [-9.5° (-25.53°, 12.68°) vs.-16.7° (-28.6°,-4.8°), P=0.489] between groups. There was a trend toward shorter microchannel length in the darapladib arm [0, (-4.4, 0.2) mm vs. 0.8 (-0.15, 1.9) mm, P=0.08]. Percentage of necrotic core volume was not significantly different. Conclusion Thus, long-term inhibition of endogenous Lp-PLA 2 activity with darapladib was not associated with a change in plaque progression and vulnerability indices after 6 months of therapy, and the endogenous Lp-PLA 2 pathway may not play a direct role in the progression of early atherosclerosis in humans.

Original languageEnglish (US)
Pages (from-to)104-113
Number of pages10
JournalCoronary Artery Disease
Volume29
Issue number2
DOIs
StatePublished - Jan 1 2018

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1-Alkyl-2-acetylglycerophosphocholine Esterase
Macrophages
Lipids
Near-Infrared Spectroscopy
Optical Coherence Tomography
Coronary Angiography
darapladib
Atherosclerosis
Histology
Ischemia
Placebos
Therapeutics

Keywords

  • atherosclerosis
  • darapladib
  • intracoronary imaging
  • intravascular imaging
  • lipoprotein-associated phospholipase A 2

ASJC Scopus subject areas

  • Cardiology and Cardiovascular Medicine

Cite this

Long-term darapladib use does not affect coronary plaque composition assessed using multimodality intravascular imaging modalities : A randomized-controlled study. / Choi, Woong Gil; Prasad, Megha; Lennon, Ryan; Gulati, Rajiv; Prasad, Abhiram; Lerman, Lilach O; Lerman, Amir.

In: Coronary Artery Disease, Vol. 29, No. 2, 01.01.2018, p. 104-113.

Research output: Contribution to journalArticle

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abstract = "Background Lipoprotein-associated phospholipase A 2 (Lp-PLA 2) may play a role in plaque progression and vulnerability. We aimed to define plaque characteristics on multimodality intravascular imaging in patients with coronary endothelial dysfunction in response to long-term inhibition of Lp-PLA2 by darapladib. Patients and methods This is a double-blinded, randomized study screening 70 patients, and enrolling 54 patients with suspected ischemia, without obstructive disease on angiography and with coronary endothelial dysfunction by invasive assessment. Patients were randomized to receive darapladib or placebo for 6 months. Forty patients underwent multimodality intravascular imaging at baseline and after 6 months of therapy. Several parameters of plaque vulnerability were measured, including maximum value of lipid core burden index for any of the 4-mm segment (maxLCBI 4 mm) by near-infrared spectroscopy. Microchannels and macrophages were assessed using optical coherence tomography and necrotic core volume by virtual histology intravascular ultrasound. Results There was no significant difference in maxLCBI 4 mm [64.56 (7.74, 128.56) vs. 22.43 (0, 75.63), P=0.522] or in macrophage images angle [-9.5° (-25.53°, 12.68°) vs.-16.7° (-28.6°,-4.8°), P=0.489] between groups. There was a trend toward shorter microchannel length in the darapladib arm [0, (-4.4, 0.2) mm vs. 0.8 (-0.15, 1.9) mm, P=0.08]. Percentage of necrotic core volume was not significantly different. Conclusion Thus, long-term inhibition of endogenous Lp-PLA 2 activity with darapladib was not associated with a change in plaque progression and vulnerability indices after 6 months of therapy, and the endogenous Lp-PLA 2 pathway may not play a direct role in the progression of early atherosclerosis in humans.",
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AU - Choi, Woong Gil

AU - Prasad, Megha

AU - Lennon, Ryan

AU - Gulati, Rajiv

AU - Prasad, Abhiram

AU - Lerman, Lilach O

AU - Lerman, Amir

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N2 - Background Lipoprotein-associated phospholipase A 2 (Lp-PLA 2) may play a role in plaque progression and vulnerability. We aimed to define plaque characteristics on multimodality intravascular imaging in patients with coronary endothelial dysfunction in response to long-term inhibition of Lp-PLA2 by darapladib. Patients and methods This is a double-blinded, randomized study screening 70 patients, and enrolling 54 patients with suspected ischemia, without obstructive disease on angiography and with coronary endothelial dysfunction by invasive assessment. Patients were randomized to receive darapladib or placebo for 6 months. Forty patients underwent multimodality intravascular imaging at baseline and after 6 months of therapy. Several parameters of plaque vulnerability were measured, including maximum value of lipid core burden index for any of the 4-mm segment (maxLCBI 4 mm) by near-infrared spectroscopy. Microchannels and macrophages were assessed using optical coherence tomography and necrotic core volume by virtual histology intravascular ultrasound. Results There was no significant difference in maxLCBI 4 mm [64.56 (7.74, 128.56) vs. 22.43 (0, 75.63), P=0.522] or in macrophage images angle [-9.5° (-25.53°, 12.68°) vs.-16.7° (-28.6°,-4.8°), P=0.489] between groups. There was a trend toward shorter microchannel length in the darapladib arm [0, (-4.4, 0.2) mm vs. 0.8 (-0.15, 1.9) mm, P=0.08]. Percentage of necrotic core volume was not significantly different. Conclusion Thus, long-term inhibition of endogenous Lp-PLA 2 activity with darapladib was not associated with a change in plaque progression and vulnerability indices after 6 months of therapy, and the endogenous Lp-PLA 2 pathway may not play a direct role in the progression of early atherosclerosis in humans.

AB - Background Lipoprotein-associated phospholipase A 2 (Lp-PLA 2) may play a role in plaque progression and vulnerability. We aimed to define plaque characteristics on multimodality intravascular imaging in patients with coronary endothelial dysfunction in response to long-term inhibition of Lp-PLA2 by darapladib. Patients and methods This is a double-blinded, randomized study screening 70 patients, and enrolling 54 patients with suspected ischemia, without obstructive disease on angiography and with coronary endothelial dysfunction by invasive assessment. Patients were randomized to receive darapladib or placebo for 6 months. Forty patients underwent multimodality intravascular imaging at baseline and after 6 months of therapy. Several parameters of plaque vulnerability were measured, including maximum value of lipid core burden index for any of the 4-mm segment (maxLCBI 4 mm) by near-infrared spectroscopy. Microchannels and macrophages were assessed using optical coherence tomography and necrotic core volume by virtual histology intravascular ultrasound. Results There was no significant difference in maxLCBI 4 mm [64.56 (7.74, 128.56) vs. 22.43 (0, 75.63), P=0.522] or in macrophage images angle [-9.5° (-25.53°, 12.68°) vs.-16.7° (-28.6°,-4.8°), P=0.489] between groups. There was a trend toward shorter microchannel length in the darapladib arm [0, (-4.4, 0.2) mm vs. 0.8 (-0.15, 1.9) mm, P=0.08]. Percentage of necrotic core volume was not significantly different. Conclusion Thus, long-term inhibition of endogenous Lp-PLA 2 activity with darapladib was not associated with a change in plaque progression and vulnerability indices after 6 months of therapy, and the endogenous Lp-PLA 2 pathway may not play a direct role in the progression of early atherosclerosis in humans.

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KW - intracoronary imaging

KW - intravascular imaging

KW - lipoprotein-associated phospholipase A 2

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