Context 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.
Objective We assessed the effect of intravenous recombinant ApoA-I Milano/phospholipid
complexes (ETC-216) on atheroma burden in patients with acute coronary syndromes
Design 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).
Setting Ten community and tertiary care hospitals in the United States.
Patients Between November 2001 and March 2003, 123 patients aged 38 to 82 years
consented, 57 were randomly assigned, and 47 completed the protocol.
Interventions 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.
Main Outcome Measures 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.
Results 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%; P = .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%; P = .97 compared with baseline). The absolute reduction in atheroma
volume in the combined treatment groups was −14.1 mm3 or
a 4.2% decrease from baseline (P<.001).
Conclusions 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.