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(Circulation. 2005;112:2792-2798.)
© 2005 American Heart Association, Inc.

Coronary Heart Disease

Pioglitazone Reduces Neointima Volume After Coronary Stent Implantation

A Randomized, Placebo-Controlled, Double-Blind Trial in Nondiabetic Patients

Nikolaus Marx, MD^*; Jochen Wöhrle, MD^*; Thorsten Nusser, MD^*; Daniel Walcher, MD; Angelika Rinker, MS; Vinzenz Hombach, MD; Wolfgang Koenig, MD; Martin Höher, MD

From the Department of Internal Medicine II, Cardiology, University of Ulm, Ulm, Germany.

Correspondence to Wolfgang Koenig, MD, Department of Internal Medicine II, Cardiology, University of Ulm, Robert-Koch-Strasse 8, D-89081 Ulm, Germany. E-mail wolfgang.koenig{at}medizin.uni-ulm.de

Received January 12, 2005; revision received June 6, 2005; accepted June 7, 2005.

Background— Restenosis requiring reintervention limits the long-term success after coronary stent implantation. Thiazolidinediones, like pioglitazone or rosiglitazone, are oral antidiabetic drugs with additional antirestenotic properties. In a randomized, placebo-controlled, double-blind trial, we examined the effect of 6-month pioglitazone therapy on neointima volume after coronary stenting in nondiabetic coronary artery disease patients.

Methods and Results— Fifty nondiabetic patients after coronary stent implantation were randomly assigned to pioglitazone (30 mg daily; pio) or placebo (control) treatment in addition to standard therapy, and neointima volume was assessed by intravascular ultrasound at the 6-month follow-up. Both groups were comparable with regard to baseline characteristics, angiographic lesion morphology, target vessel, and length of the stented segment. In addition, there were no statistical differences in minimal lumen diameter before and after intervention, as well as reference diameter after stent implantation. In this study population of nondiabetic patients, pio treatment did not significantly change fasting blood glucose, fasting insulin, or glycosylated hemoglobin levels, as well as lipid parameters. In contrast, pio treatment significantly reduced neointima volume within the stented segment, with 2.3±1.1 mm³/mm in the pio group versus 3.1±1.6 mm³/mm in controls (P=0.04). Total plaque volume (adventitia-lumen area) was significantly lower at follow-up in the pio group (11.2±3.2 mm³/mm) compared with controls (13.2±4.2 mm³/mm; P=0.04). Moreover, the binary restenosis rate was 3.4% in the pio group versus 32.3% in controls (P<0.01).

Conclusions— Thus, 6-month treatment with pio significantly reduced neointima volume after coronary stent implantation in nondiabetic patients. These data bolster the hypothesis that antidiabetic thiazolidinediones, in addition to their metabolic effects, exhibit direct antirestenotic effects in the vasculature.

Key Words: stents • thiazolidinediones • intima • coronary disease • diabetes mellitus

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