Effects of the direct lipoprotein-associated phospholipase A(2) inhibitor darapladib on human coronary atherosclerotic plaque

Serruys, P. W. and García-García, H. M. and Buszman, P. and Erne, P. and Verheye, S. and Aschermann, M. and Duckers, H. and Bleie, O. and Dudek, D. and Bøtker, H. E. and von Birgelen, C. and D'Amico, D. and Hutchinson, T. and Zambanini, A. and Mastik, F. and van Es, G. A. and van der Steen, A. F. and Vince, D. G. and Ganz, P. and Hamm, C. W. and Wijns, W. and Zalewski, A. and Integrated, Biomarker. (2008) Effects of the direct lipoprotein-associated phospholipase A(2) inhibitor darapladib on human coronary atherosclerotic plaque. Circulation, Vol. 118, H. 11. pp. 1172-1182.

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Official URL: http://edoc.unibas.ch/dok/A6003661

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BACKGROUND: Lipoprotein-associated phospholipase A(2) (Lp-PLA(2)) is expressed abundantly in the necrotic core of coronary lesions, and products of its enzymatic activity may contribute to inflammation and cell death, rendering plaque vulnerable to rupture. METHODS AND RESULTS: This study compared the effects of 12 months of treatment with darapladib (an oral Lp-PLA(2) inhibitor, 160 mg daily) or placebo on coronary atheroma deformability (intravascular ultrasound palpography) and plasma high-sensitivity C-reactive protein in 330 patients with angiographically documented coronary disease. Secondary end points included changes in necrotic core size (intravascular ultrasound radiofrequency), atheroma size (intravascular ultrasound gray scale), and blood biomarkers. BACKGROUND: =0.37). In contrast, Lp-PLA(2) activity was inhibited by 59% with darapladib (P>0.001 versus placebo). After 12 months, there were no significant differences between groups in plaque deformability (P=0.22) or plasma high-sensitivity C-reactive protein (P=0.35). In the placebo-treated group, however, necrotic core volume increased significantly (4.5+/-17.9 mm(3); P=0.009), whereas darapladib halted this increase (-0.5+/-13.9 mm(3); P=0.71), resulting in a significant treatment difference of -5.2 mm(3) (P=0.012). These intraplaque compositional changes occurred without a significant treatment difference in total atheroma volume (P=0.95). CONCLUSIONS: Despite adherence to a high level of standard-of-care treatment, the necrotic core continued to expand among patients receiving placebo. In contrast, Lp-PLA(2) inhibition with darapladib prevented necrotic core expansion, a key determinant of plaque vulnerability. These findings suggest that Lp-PLA(2) inhibition may represent a novel therapeutic approach.
Faculties and Departments:03 Faculty of Medicine > Departement Biomedizin > Further Research Groups at DBM > Signal Transduction (Resink/Erne)
UniBasel Contributors:Erne, Paul
Item Type:Article, refereed
Article Subtype:Research Article
Publisher:Lippincott Williams & Wilkins
Note:Publication type according to Uni Basel Research Database: Journal article
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Last Modified:08 Nov 2012 16:23
Deposited On:08 Nov 2012 16:18

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