A prospective, multicenter, randomized trial to assess efficacy of pioglitazone on in-stent neointimal suppression in type 2 diabetes: POPPS (Prevention of In-Stent Neointimal Proliferation by Pioglitazone Study)

The aim of this study was to clarify whether pioglitazone suppresses in-stent neointimal proliferation and reduces restenosis and target lesion revascularization (TLR) after percutaneous coronary intervention (PCI). Previous single-center studies have demonstrated the anti-restenotic effect of a peroxisome proliferator-activated receptor gamma agonist, pioglitazone, after PCI. A total of 97 patients with type 2 diabetes mellitus (T2DM) undergoing PCI (bare-metal stents only) were enrolled. After PCI, patients were randomly assigned to either the pioglitazone group (n = 48) or the control group (n = 49). Angiographical and intravascular ultrasound (IVUS) imaging were performed at baseline and repeated at 6-month follow-up. Primary end points included angiographical restenosis and TLR at 6 months follow-up. Secondary end point was in-stent neointimal volume by IVUS. Baseline glucose level and glycosylated hemoglobin (HbA1c) level were similar between the pioglitazone group and the control group. Angiographical restenosis rate was 17% in the pioglitazone group and 35% in control group (p = 0.06). The TLR was significantly lower in pioglitazone group than in control group (12.5% vs. 29.8%, p = 0.04). By IVUS (n = 56), in-stent neointimal volume at 6 months showed a trend toward smaller in the pioglitazone group than in the control group (48.0 +/- 30.2 mm(3) vs. 62.7 +/- 29.0 mm(3), p = 0.07). Neointimal index (neointimal volume/stent volume x 100) was significantly smaller in the pioglitazone group than in the control group (31.1 +/- 14.3% vs. 40.5 +/- 12.9%, p = 0.01). Pioglitazone treatment might suppress in-stent neointimal proliferation and reduce incidence of TLR after PCI in patients with T2DM.