Effects of Pioglitazone on coronary atherosclerotic plaque composition and plaque progression in non-diabetic patients: a double-center, randomized controlled VH-IVUS pilot-trial

Abstract

Background: Despite the advanced therapy with statins, antithrombotics and an-tihypertensive agents, the medical treatment of coronary artery disease is less than optimal. Therefore, additional therapeutic anti-atherosclerotic options are desirable. This VH-IVUS study (intravascular ultrasonography with virtual histology) was performed to assess the potential anti-atherogenic effect of Pioglitazone in non-diabetic patients. Methods and results: A total of 86 non-culprit atherosclerotic lesions in 54 patients with acute coronary syndrome were observed in a nine-month prospective, double-blind, and placebo-controlled IVUS-study. Patients were randomized to receive either 30 mg Pioglitazone (Pio) or placebo (Plac). As primary efficacy parameter, the change of relative plaque content of necrotic core was determined by serial VH-IVUS analyses. Secondary endpoint was the change of total plaque volume. Further effects of Pioglitazone such as biochemical and clinical vessel function markers as surrogate parameters for the cardiovascular outcome were determined. In contrast to placebo, in the Pioglitazone-treated group, the relative plaque content of necrotic core decreased significantly (Pio -1.3±6.9% vs Plac +2.6±6.5%, p<0.01). In comparison to the placebo group, the plaques in Pioglitazone-treated patients showed significantly greater reduction of the total plaque volume (Pio -16.1±26.4 mm3 vs. Plac -1.8±30.9 mm3, p=0.02). Except the tendency to a reduction of systemic inflammatory markers (high sensitive C-reactive protein and white blood count), no further clinical parameters including carotid intima-media thickness, pulse wave velocity and retinal vessel analysis showed relevant changes after Pioglitazone treatment. (figure Presented) Conclusions: Treatment with Pioglitazone in non-diabetic patients results in a coronary artery plaque stabilization on top of usual medical care.