title: Effects of the direct lipoprotein-associated phospholipase A(2) inhibitor darapladib on human coronary atherosclerotic plaque.
abstract: 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.
  
  
  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.
authors.affiliation: Thoraxcenter, Ba583, Erasmus MC, Rotterdam, Netherlands. p.w.j.c.serruys@erasmusmc.nl
authors.forename: Patrick W
authors.initials: PW
authors.lastname: Serruys
authors.forename: Héctor M
authors.initials: HM
authors.lastname: García-García
authors.forename: Pawel
authors.initials: P
authors.lastname: Buszman
authors.forename: Paul
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authors.lastname: Erne
authors.forename: Stefan
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authors.lastname: Verheye
authors.forename: Michael
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authors.lastname: Aschermann
authors.forename: Henrikus
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authors.lastname: Duckers
authors.forename: Oyvind
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authors.lastname: Bleie
authors.forename: Dariusz
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authors.lastname: Dudek
authors.forename: Hans Erik
authors.initials: HE
authors.lastname: Bøtker
authors.forename: Clemens
authors.initials: C
authors.lastname: von Birgelen
authors.forename: Don
authors.initials: D
authors.lastname: D'Amico
authors.forename: Tammy
authors.initials: T
authors.lastname: Hutchinson
authors.forename: Andrew
authors.initials: A
authors.lastname: Zambanini
authors.forename: Frits
authors.initials: F
authors.lastname: Mastik
authors.forename: Gerrit-Anne
authors.initials: GA
authors.lastname: van Es
authors.forename: Antonius F W
authors.initials: AF
authors.lastname: van der Steen
authors.forename: D Geoffrey
authors.initials: DG
authors.lastname: Vince
authors.forename: Peter
authors.initials: P
authors.lastname: Ganz
authors.forename: Christian W
authors.initials: CW
authors.lastname: Hamm
authors.forename: William
authors.initials: W
authors.lastname: Wijns
authors.forename: Andrew
authors.initials: A
authors.lastname: Zalewski