Effect of recombinant ApoA-I Milano on coronary atherosclerosis in patients with acute coronary syndromes: a randomized controlled trial.
BACKGROUND
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 (ACS).


METHODS
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).


METHODS
Ten community and tertiary care hospitals in the United States.


METHODS
Between November 2001 and March 2003, 123 patients aged 38 to 82 years consented, 57 were randomly assigned, and 47 completed the protocol.


METHODS
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.


METHODS
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.
Nissen
Steven E
SE
Department of Cardiovascular Medicine, Cleveland Clinic Foundation, Cleveland, Ohio 44195, USA. nissens@ccf.org
Tsunoda
Taro
T
Tuzcu
E Murat
EM
Schoenhagen
Paul
P
Cooper
Christopher J
CJ
Yasin
Muhammad
M
Eaton
Gregory M
GM
Lauer
Michael A
MA
Sheldon
W Scott
WS
Grines
Cindy L
CL
Halpern
Stephen
S
Crowe
Tim
T
Blankenship
James C
JC
Kerensky
Richard
R
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000789:Angina, Unstable / Q000188:drug therapy*; D016632:Apolipoprotein A-I / Q000008:administration & dosage / Q000627:therapeutic use*; D017023:Coronary Angiography; D003324:Coronary Artery Disease / Q000000981:diagnostic imaging / Q000188:drug therapy* / Q000503:physiopathology; D004311:Double-Blind Method; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D009203:Myocardial Infarction / Q000188:drug therapy*; D010713:Phosphatidylcholines / Q000008:administration & dosage / Q000627:therapeutic use*; D011446:Prospective Studies; D018084:Ultrasonography, Interventional
D016632:Apolipoprotein A-I; C474616:ETC216; D010713:Phosphatidylcholines; C080631:apolipoprotein A-I Milano