Restenosis after
stent deployment remains a major clinical problem.
Antioxidants have been proposed as a promising strategy against restenosis. We tested the
antioxidant probucol for its efficacy against neointimal
hyperplasia in porcine coronary arteries after
stent implantation.
Probucol was then tested in vivo in 8 coronary arteries of 4 pigs (1000 mg/day orally beginning 7 days before stenting) and was compared to placebo (10 coronary arteries, 5 pigs) 28 days after stenting. Quantitative intravascular ultrasound (IVUS) revealed 38.8 +/- 4.0 versus 40.1 +/- 3.0% area
stenosis in the
probucol versus control group. Histopathologic assessment showed that
probucol had no beneficial effect on inhibiting the neointimal proliferative response in
stent lesions compared to placebo (2.35 +/- 0.26 versus 2.88 +/- 0.25 mm(2)), despite similar injury scores (1.20 +/- 0.12 versus 1.28 +/- 0.14). An edge segment (axially 2-mm proximal to the
stent margins) was assessed by IVUS. Remodeling index, which is a good marker of constrictive remodeling, was defined by the ratio of the vessel area in the lesion site (
stent edge) to the vessel area in the proximal reference site (6-mm proximal to the
stent margins). The remodeling index was significantly larger in the
probucol group that in the placebo group (1.18 +/- 0.10 versus 0.90 +/- 0.06, P = 0.0012). In conclusion,
probucol reduced constrictive remodeling at the edge of the implant but did not inhibit the tissue response within the
stent.