Although the role of inflammation in the pathophysiology of coronary artery disease (CAD) is undisputable, whether lowering inflammation processes would result in cardiovascular benefits is still unknown. In the Integrated Biomarker and Imaging Study-2 (IBIS-2), Serruys et al. tested the hypothesis that inhibition of a specific inflammatory marker (lipoprotein-associated phospholipase A2 [Lp-PLA2]), would spur improvements in plaque deformability. As Lp-PLA2 promotes several pro-inflammatory and pro-oxidant reactions within the necrotic core, the efficacy of a specific Lp-PLA2 inhibitor, darapladib, was tested. In this 12-month trial, 330 patients with CAD and elevated plasma C-reactive protein concentrations were randomized to receive either darapladib (160 mg/day) or placebo. Although Lp-PLA2 activity decreased by 59% in the darapladib arm, the primary endpoint of plaque deformability was similar between the two groups at the end of treatment. However, the authors reported that other markers of plaque composition/stability improved. Among these secondary endpoints, necrotic core volume, a determinant of plaque vulnerability, progressed only in patients under placebo. Based on the observation that pharmacological intervention with darapladib has favourable effects on coronary atheroma, the authors concluded that Lp-PLA2 inhibition may represent a novel therapeutic approach to reduce residual risk in CAD patients.
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