Thiazolidinediones (TZDs) are peroxisome proliferator activated receptors (PPAR)-gamma agonists. They decrease insulin resistance, levels of CRP, fibrinogen, LDL-cholesterol, triglycerides and resistin in comparison with placebo [
17,
41]. TZDs inhibit VSMC proliferation, ameliorating intimal hyperplasia and restenosis [
42]. Under high glucose conditions the inhibitory activity of VSMC proliferation by pioglitazone and rosiglitazone is enhanced, in contract to troglitazone [
42].
Several studies have suggested the preventive effects of TZDs on atherosclerosis, restenosis, in-stent restenosis, and reocclusion after PCI in patients with type 2 diabetes. Takagi et al (2002) showed in a randomized study that in 55 patients with 60 lesions troglitazone was associated with reduced angiographic in-stent restenosis and neointimal tissue proliferation [
43]. Choi et al (2004) found in a case-control study with 83 patients treated with rosiglitazone that at 6 months a significant reduction in restenosis rate, greater minimal lumen stent diameter and albeit non-significant lower TVR [
44]. Nishio et al (2006) observed in randomized study with 54 patients that treatment with pioglitazone attenuated neointimal thickening regardless of the type of PCI and resulted in less late luminal loss [
45]. The meta-analysis of Rosmarakis et al in 2007 already showed that TZDs decrease the need for target vessel revascularization when 5 trials with 235 patients were analyzed [
46]. The meta-analysis by Geng et al published in 2009 consisted of 8 trials with 366 patients and showed that TZDs were associated with a significant reduction in the risk of in-stent restenosis in both diabetic and non-diabetic patients [
47]. They also observed a reduction in late lumen loss, percent diameter stenosis, neointimal area/volume, and target lesion revascularization. Recently, Finn et al (2009) randomly assigned 65 diabetics to rosiglitazone or placebo and could not confirm the above described results on luminal loss [
48]. An interesting observation was made by Nishio et al (2006), i.e. that in 38 type 2 diabetics similar restenosis rates were present in patients treated with either a BMS with pioglitazone or sirolimus-eluting stent without pioglitazone [
49]. Fang et al (2007) demonstrated that rosiglitazone therapy in comparison to standard antidiabetic therapy without rosiglitazone in type 2 diabetics leads to a significant decrease in restenosis and mortality [
50]. However, the intervention group significantly used more insulin and biguanides, which might lead to bias of the observed effects. In a study with 417 patients referred for stress testing to evaluate chest pain by Kapinya et al (2008), 222 were treated with conventional therapy only (insulin and insulin secretagogues) and 195 as being treated with insulin sensitizers (metformin and thiazolidinediones) [
51]. The rate of ischemia and MI was not significantly lower in patients treated with thiazolidinediones. In the Pioglitazone Effect on Regression of Intravascular Sonographic Coronary Obstruction Prospective Evaluation (PERISCOPE)-trial, Nissen et al (2008) demonstrated that in patients with type 2 diabetes and coronary artery disease treatment with pioglitazone compared with glimepiride results in a significantly lower rate of progression of coronary atherosclerosis, as measured with intravascular ultrasound [
52]. The patients receiving pioglitazone also had significantly reduced levels of CRP, triglycerides and HbA1c and an increase in HDL. Nonetheless, this trial did not show any significant differences in clinical outcome between pioglitazone and glimepiride. Recently, Clementi et al (2009) demonstrated in 25 patients with diabetes that administration of pioglitazone combined with atorvastatin leads to a significant regression of coronary atherosclerosis [
53].