Reduction of neointimal hyperplasia after coronary stenting by pioglitazone in nondiabetic patients with metabolic syndrome

Abstract

This study investigates whether pioglitazone reduces neointimal hyperplasia after coronary stenting in nondiabetic patients with metabolic syndrome (MS) using intravascular ultrasound (IVUS). Pioglitazone, a novel insulin-sensitizing thiazolidinedione, has been shown to reduce neointimal hyperplasia after coronary stenting in patients with type 2 diabetes. However, the effect of pioglitazone on in-stent restenosis in nondiabetic patients with MS remains unknown. Twenty-eight nondiabetic patients with MS after bare-metal stent implantation were randomized to 6-month treatment with or without 30 mg/d of pioglitazone (pioglitazone group [PIO] of 14 patients with 16 lesions and control group [CONT] of 14 patients with 16 lesions). At baseline and at 6-month follow-up, assessment of insulin resistance and visceral fat accumulation, quantitative coronary angiographic analysis, and IVUS measurements were performed. Pioglitazone treatment improved insulin resistance and decreased visceral fat accumulation without significant changes in plasma glucose levels, glycosylated hemoglobin A1c levels, and lipid profiles. Intimal index (intimal area/stent area) and intimal area were reduced in PIO compared with CONT (13% +/- 7% vs 21% +/- 13%, P = .033; 1.28 +/- 0.76 mm2 vs 1.90 +/- 1.16 mm2, P = .084; respectively). Binary restenosis rate was 0% in PIO versus 31% in CONT (P = .043). This is the first randomized, prospective IVUS study demonstrating that pioglitazone reduces neointimal hyperplasia after coronary stenting in nondiabetic patients with MS. Our data suggest that pioglitazone treatment may represent a novel therapeutic tool to target in-stent restenosis in nondiabetic patients with MS.