Darapladib inhibits necrotic core expansion in atherosclerotic lesions

Serruys PW et al. (2008) Effects of direct lipoprotein-associated phospholipase A2 inhibitor darapladib on human coronary atherosclerotic plaque. Circulation 118: 1172–1182

Results from the second Integrated Biomarker and Imaging Study published in Circulation reveal that treatment with the direct lipoprotein-associated phospholipase A₂ (Lp-PLA₂) inhibitor, darapladib, slows the progression of atherosclerotic core expansion when compared with placebo.

In this international, double-blind trial, eligible patients scheduled to undergo cardiac catheterization for an acute coronary syndrome, or chest pain of other etiology, were randomly assigned to receive 160 mg daily of darapladib (n = 175) or placebo (n = 155) for 12 months. In total, 131 darapladib-treated and 115 placebo-treated patients completed treatment and underwent intravascular ultrasound imaging (median follow-up 364 days). Necrotic core volumes of the imaged atherosclerotic lesions increased significantly during the study period among patients who received placebo, but remained unchanged from baseline in those who received darapladib (P = 0.012 for between-group comparison). The change in total atheroma volume from baseline did not differ significantly between the two treatment groups. In addition, plasma levels of Lp-PLA₂ at 12 months were 59% lower with darapladib treatment than with placebo (P <0.001). The mean on-treatment systolic blood pressure was 3 mmHg higher in the darapladib group than in the placebo group (P = 0.031), but no other significant differences in clinical outcome or in the number of adverse events were observed. The authors suggest that Lp-PLA₂ inhibition could represent a novel therapeutic approach for patients with atherosclerosis.