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.
RCT Entities:
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.
Authors: Hongfeng Wang; Dorothee Weihrauch; Judy R Kersten; Jeffrey M Toth; Anthony G Passerini; Anita Rajamani; Sonja Schrepfer; John F LaDisa Journal: Am J Physiol Heart Circ Physiol Date: 2015-08-07 Impact factor: 4.733
Authors: Manabu Fujita; Natalya M Khazenzon; Alexander V Ljubimov; Bong-Seop Lee; Ismo Virtanen; Eggehard Holler; Keith L Black; Julia Y Ljubimova Journal: Angiogenesis Date: 2006-11-16 Impact factor: 9.596