The selective Lp-PLA2 (lipoprotein-associated phospholipase A2) inhibitor darapladib, in addition to standard of care treatment, prevented expansion of the necrotic core, a region associated with a high risk of rupture, according to the results of the IBIS-2 trial presented Tuesday at the European Society of Cardiology (ESC) congress in Munich, Germany.
When the results of IBIS-2 (Integrated Biomarkers and Imaging Study-2) were presented on GlaxoSmithKline’s investigative Lp-PLA2, they were published simultaneously in Circulation.
The IBIS-2 study was a one-year international, randomized, placebo-controlled, parallel-group study in 330 subjects with angiographically documented coronary heart disease, according to the researchers. They noted that the study was not powered to address the effects of darapladib on cardiovascular outcomes. IBIS-2 used Volcano's virtual histology intravascular ultrasound, which allowed physicians to acquire images of diseased vessels from inside the artery and to acquire data on plaque composition and deformability.
According to the Phase II exploratory IBIS-2 trial showed that the co-primary endpoints of plaque deformability and plasma levels of hsCRP, showed no significant differences between darapladib and placebo treatment groups, but trended positively.
However, the researchers reported that the key secondary endpoints showed significant effects of darapladib on plaque composition and plasma levels of Lp-PLA2 activity: On average, after 12 months, patients treated with placebo experienced a significant increase in necrotic core volume, while expansion of the necrotic core was halted in the darapladib-treated group. This resulted in a significant treatment difference in favor of darapladib. The effect of darapladib on necrotic core was consistent among several subgroups.
The investigators also said that the activity of circulating Lp-PLA2 was reduced by 59 percent.
They also reported a higher incidence of malodor (mainly feces or urine) with darapladib (16 percent) compared with placebo (3 percent), but was not a common cause of withdrawal from the study (darapladib: 2 percent).
“With darapladib added to current standard therapies, our study suggests that the potential plaque-stabilizing effects of darapladib may represent an important approach in treating atherosclerosis and reducing cardiovascular risk,” said Chairman of the IBIS-2 Steering Committee Patrick Serruys, MD, PhD, professor of medicine at the Erasmus University, Rotterdam, the Netherlands.