Role of probucol in inhibiting intimal hyperplasia after coronary stent implantation: A randomized study

Abstract

Oxygen-free radicals can stimulate smooth muscle cell proliferation and may therefore be involved in the genesis of in-stent restenosis. Thus, treatment with probucol, a potent antioxidant agent that has been shown to reduce restenosis after balloon angioplasty, may be an effective strategy to prevent intimal hyperplasia after stenting. In a prospective double-blind study, 59 patients submitted to coronary stent implantation were randomly assigned to treatment with either probucol (1 g/d) or placebo, starting two weeks before the procedure and continued for 6 months. The primary end point was the intimal hyperplasia volume at 6 months measured by intravascular ultrasound (IVUS) imaging. Of the 59 randomized patients, 54 underwent successful stent implantation, completed the follow-up period, and underwent repeat angiography, 6.1 +/- 1.1 months after the procedure. Volumetric IVUS analysis revealed similar intimal hyperplasia volumes (403 +/- 26.7 mm3 for probucol vs 44.8 +/- 28.3 mm3 for placebo) and percent volume obstruction of the lumen (30.4% +/- 14.5% for probucol versus 30.7% +/- 17.2% for placebo) in both groups. In addition, quantitative coronary angiography showed no differences in late loss (1.0 +/- 0.8 mm vs 1.1 +/- 0.8 mm), loss index (0.5 +/- 0.4 for both groups), or angiographic restenosis rates (19.4% vs 18.5%) between the probucol and placebo groups, despite the observation of significant changes in the lipid profile and in the plasma antioxidant defenses in patients receiving probucol. Treatment with the antioxidant probucol failed to reduce neointimal formation after coronary stent implantation as assessed by IVUS volumetric analysis.