Local intracoronary administration of antisense oligonucleotide against c-myc for the prevention of in-stent restenosis: results of the randomized investigation by the Thoraxcenter of antisense DNA using local delivery and IVUS after coronary stenting (ITALICS) trial.
OBJECTIVE
This study was designed to determine whether antisense oligodeoxynucleotides (ODN) directed against the nuclear proto-oncogene c-myc could inhibit restenosis when given by local delivery immediately after coronary stent implantation.


BACKGROUND
Failure of conventional pharmacologic therapies to reduce the incidence of coronary restenosis after percutaneous revascularization techniques has prompted interest in the use of agents that target intracellular central regulatory mechanisms.


METHODS
Eighty-five patients were randomly assigned to receive either 10 mg of phosphorothioate-modified 15-mer antisense ODN or saline vehicle by intracoronary local delivery after coronary stent implantation. The primary end point was percent neointimal volume obstruction measured by computerized analysis of electrocardiogram-gated intravascular ultrasound (IVUS) at six-month follow-up. Secondary end points included clinical outcome and quantitative coronary angiography analysis.


RESULTS
Analysis of follow-up IVUS data was performed on 77 patients. In-stent volume obstruction was similar between groups (44 +/- 16% and 46 +/- 14%, placebo vs. ODN; p = 0.57; 95% confidence interval: -1.13 to 0.85). Minimum luminal diameter increased from 0.84 +/- 0.36 and 0.90 +/- 0.45 (p = 0.55) to 2.70 +/- 0.37 and 2.80 +/- 0.37 (p = 0.28) after stent implantation, which decreased to 1.50 +/- 0.61 and 1.50 +/- 0.53 (p = 0.98) by six months, yielding similar loss indexes (placebo vs. ODN, respectively). There were no differences in angiographic restenosis rates (38.5 and 34.2%; p = 0.81; placebo vs. ODN) or clinical outcome.


CONCLUSIONS
Treatment with 10 mg of phosphorothioate-modified ODN directed against c-myc does not reduce neointimal volume obstruction or the angiographic restenosis rate in this patient population.
Kutryk
Michael J B
MJ
Department of Interventional Cardiology, Thoraxcenter, University Hospital Dijkzigt, Rotterdam, The Netherlands.
Foley
David P
DP
van den Brand
Marcel
M
Hamburger
Jaap N
JN
van der Giessen
Willem J
WJ
deFeyter
Pim J
PJ
Bruining
Nico
N
Sabate
Manel
M
Serruys
Patrick W
PW
D000368:Aged; D023903:Coronary Restenosis / Q000000981:diagnostic imaging / Q000235:genetics / Q000517:prevention & control*; D016503:Drug Delivery Systems; D005260:Female; D016259:Genes, myc / Q000187:drug effects*; D006801:Humans; D008297:Male; D008875:Middle Aged; D009841:Oligonucleotides / Q000008:administration & dosage*; D000090063:Proto-Oncogene Mas; D015607:Stents; D018084:Ultrasonography, Interventional
C434123:LR-3280; C000715470:MAS1 protein, human; D009841:Oligonucleotides; D000090063:Proto-Oncogene Mas