High-density lipoprotein (HDL) plays a key role in reverse
cholesterol transport but also activates
nitric oxide synthase and stimulates
prostacyclin release, enhances endothelial repair, inhibits
cell adhesion molecule expression on vascular endothelium and monocyte recruitment into the arterial wall, and exerts antithrombotic effects. In experimental animals, infusions of HDL or
apolipoprotein A-1 (apoA-1) halt the progression or induce regression of
atherosclerosis, with favorable effects on plaque composition. Remarkably, a benefit is observed after a single infusion. In a pilot study, weekly infusions of
ETC-216, a formulation of recombinant
apoA-1 Milano, were administered at two doses for 5 weeks to patients beginning within 2 weeks of an
acute coronary syndrome (ACS). Among the 47 patients completing the study, percent
atheroma volume by intracoronary ultrasound was reduced in the combined active treatment groups but not in the placebo group. In a larger trial, the Effect of rHDL on
Atherosclerosis-Safety and efficacy (ERASE), 183 post-ACS patients were randomized to 4 weekly infusions of placebo or one of two doses of
CSL-111, which consists of
apoA-1 derived from human plasma and combined with soybean
phosphatidylcholine. The greater dose was discontinued because of a high incidence of hepatic
enzyme elevation. Among the 136 patients with evaluable end point data, percent change in
atheroma volume, the primary endpoint, improved significantly in the
CSL-111 group but not in the placebo group. The secondary end points of plaque characterization indices and quantitative coronary angiographic changes both improved significantly in the
CSL-111 group compared with the group receiving placebo. Taken together, this evidence suggests that infusions of HDL or
apoA-1 may reduce events, particularly among patients with ACS.