Inhibition of lipoprotein-associated phospholipase activity by darapladib: shifting gears in cardiovascular drug development: are antiinflammatory drugs the next frontier?

Description

The results of the IBIS-2 trial were commented by Boekholdt et al. from the Academic Medical Centre in Amsterdam, the Netherlands. The authors described the biological and epidemiological data supporting the potential role of Lp-PLA2 as an important risk marker for CAD. They concluded that the evidence was equivocal because Lp-PLA2 can have both pro-atherogenic and anti-atherogenic properties. When commenting on the paper by Serruys et al., the authors highlighted the fact that plasma levels of oxidized LDL (oxLDL) were not measured. The authors considered this a limitation, given the well-described relationship between this marker and Lp-PLA2, and therefore could not investigate whether oxLDL could have modulated the reported treatment effect. In addition, they established the pros and cons of using this “new” technique to evaluate plaque composition, which differs from established intravascular ultrasound-based methods. They also mentioned that changes in these surrogate CAD markers do not always translate into risk reduction and prudently concluded that the results of larger and event-driven trials are needed.