Objective: Pioglitazone has been shown to exert multiple antiatherosclerotic actions independent from its glycemic effects. We studied the hypothesis that pioglitazone improves coronary endothelial dysfunction in non-diabetic patients with coronary artery disease (CAD) in a randomized, placebo-controlled, double-blind trial.
Methods: Fifty non-diabetic patients with CAD were randomized to 6 months treatment with pioglitazone 30 mg daily or placebo. Coronary endothelial function was tested at baseline and after 6 months with intracoronary infusion of adenosine, acetylcholine (0.072; 0.72; 7.2, and 36 microg/min), glyceroltrinitrate, and cold pressor test (CPT). The primary endpoint was the mean effect of treatment compared with placebo on acetylcholine-induced coronary vascular response for all acetylcholine dosages, based on percent change in luminal area measured by quantitative coronary angiography.
Results: There was no difference in baseline coronary endothelial function. The primary endpoint was significantly different between the groups with a 1.8% +/- 2.0% increase in luminal area between baseline and follow-up with pioglitazone and a 7.6% +/- 2.4% decrease in the placebo group (P < 0.008). At follow-up, there was a trend for a difference in CPT (P = 0.057). No difference was observed regarding intracoronary glyceroltrinitrate or adenosine.
Conclusions: Pioglitazone treatment in non-diabetic patients with CAD was associated with a significantly better coronary endothelial function compared to placebo.