Title: Effect of Recombinant ApoA-I Milano on Coronary Atherosclerosis in Patients With Acute Coronary Syndromes
Abstract: <h3>Context</h3> Although low levels of high-density lipoprotein cholesterol (HDL-C) increase risk for coronary disease, no data exist regarding potential benefits of administration of HDL-C or an HDL mimetic. ApoA-I Milano is a variant of apolipoprotein A-I identified in individuals in rural Italy who exhibit very low levels of HDL. Infusion of recombinant ApoA-I Milano–phospholipid complexes produces rapid regression of atherosclerosis in animal models. <h3>Objective</h3> We assessed the effect of intravenous recombinant ApoA-I Milano/phospholipid complexes (ETC-216) on atheroma burden in patients with acute coronary syndromes (ACS). <h3>Design</h3> The study was a double-blind, randomized, placebo-controlled multicenter pilot trial comparing the effect of ETC-216 or placebo on coronary atheroma burden measured by intravascular ultrasound (IVUS). <h3>Setting</h3> Ten community and tertiary care hospitals in the United States. <h3>Patients</h3> Between November 2001 and March 2003, 123 patients aged 38 to 82 years consented, 57 were randomly assigned, and 47 completed the protocol. <h3>Interventions</h3> In a ratio of 1:2:2, patients received 5 weekly infusions of placebo or ETC-216 at 15 mg/kg or 45 mg/kg. Intravascular ultrasound was performed within 2 weeks following ACS and repeated after 5 weekly treatments. <h3>Main Outcome Measures</h3> The primary efficacy parameter was the change in percent atheroma volume (follow-up minus baseline) in the combined ETC-216 cohort. Prespecified secondary efficacy measures included the change in total atheroma volume and average maximal atheroma thickness. <h3>Results</h3> The mean (SD) percent atheroma volume decreased by −1.06% (3.17%) in the combined ETC-216 group (median, −0.81%; 95% confidence interval [CI], −1.53% to −0.34%;<i>P</i>= .02 compared with baseline). In the placebo group, mean (SD) percent atheroma volume increased by 0.14% (3.09%; median, 0.03%; 95% CI, −1.11% to 1.43%;<i>P</i>= .97 compared with baseline). The absolute reduction in atheroma volume in the combined treatment groups was −14.1 mm<sup>3</sup>or a 4.2% decrease from baseline (<i>P</i><.001). <h3>Conclusions</h3> A recombinant ApoA-I Milano/phospholipid complex (ETC-216) administered intravenously for 5 doses at weekly intervals produced significant regression of coronary atherosclerosis as measured by IVUS. Although promising, these results require confirmation in larger clinical trials with morbidity and mortality end points.