TY - JOUR
T1 - Long-term darapladib use does not affect coronary plaque composition assessed using multimodality intravascular imaging modalities
T2 - A randomized-controlled study
AU - Choi, Woong Gil
AU - Prasad, Megha
AU - Lennon, Ryan
AU - Gulati, Rajiv
AU - Prasad, Abhiram
AU - Lerman, Lilach O.
AU - Lerman, Amir
N1 - Publisher Copyright:
© 2018 Wolters Kluwer Health, Inc. All rights reserved.
PY - 2018
Y1 - 2018
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.
KW - atherosclerosis
KW - darapladib
KW - intracoronary imaging
KW - intravascular imaging
KW - lipoprotein-associated phospholipase A 2
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U2 - 10.1097/MCA.0000000000000573
DO - 10.1097/MCA.0000000000000573
M3 - Article
C2 - 29135482
AN - SCOPUS:85045082493
SN - 0954-6928
VL - 29
SP - 104
EP - 113
JO - Coronary Artery Disease
JF - Coronary Artery Disease
IS - 2
ER -