Regression of coronary atherosclerosis with infusions of the high-density lipoprotein mimetic CER-001 in patients with more extensive plaque burden

Background: CER-001 is an engineered pre-betahigh- density lipoprotein (HDL) mimetic, which rapidly mobilizes cholesterol. Infusion of CER-001 3 mg/kg exhibited a potentially favorable effect on plaque burden in the CHI-SQUARE (Can HDL Infusions Significantly Quicken Atherosclerosis Regression) study. Since baseline atheroma burden has been shown as a determinant for the efficacy of HDL infusions, the degree of baseline atheroma burden might influence the effect of CER-001. Methods: CHI-SQUARE compared the effect of 6 weekly infusions of CER-001 (3, 6 and 12 mg/kg) vs. placebo on coronary atherosclerosis in 369 patients with acute coronary syndrome (ACS) using serial intravascular ultrasound (IVUS). Baseline percent atheroma volume (B-PAV) cutoff associated with atheroma regression following CER-001 infusions was determined by receiver-operating characteristics curve analysis. 369 subjects were stratified according to the cutoff. The effect of CER-001 at different doses was compared to placebo in each group. Results: A B-PAV = 30% was the optimal cutoff associated with PAV regression following CER-001 infusions. CER-001 induced PAV regression in patients with B-PAV = 30% but not in those with B-PAV <30% (-0.45%+/- 2.65% vs. + 0.34%+/- 1.69%, P= 0.01). Compared to placebo, the greatest PAV regression was observed with CER- 001 3mg/kg in patients with B- PAV = 30% (-0.96%+/- 0.34% vs. - 0.25%+/- 0.31%, P= 0.01), whereas there were no differences between placebo (+ 0.09%+/- 0.36%) versus CER-001 in patients with B-PAV < 30% (3 mg/kg; + 0.41%+/- 0.32%, P= 0.39; 6 mg/ kg; + 0.27%+/- 0.36%, P= 0.76; 12 mg/kg; + 0.32%+/- 0.37%, P= 0.97). Conclusions: Infusions of CER-001 3 mg/kg induced the greatest atheroma regression in ACS patients with higher B-PAV. These findings identify ACS patients with more extensive disease as most likely to benefit from HDL mimetic therapy.