Candesartan With Pioglitazone Protects Against Endothelial Dysfunction and Inflammatory Responses in Porcine Coronary Arteries Implanted With Sirolimus-Eluting Stents

Abstract

Background: Sirolimus-eluting stents (SES) are widely used in coronary artery disease as revascularization therapy. Although endothelial dysfunction induced by implanted SES can become a major clinical concern, therapeutic strategies to overcome this disorder remain unclear. The aim of the present study was therefore to identify effective therapies in a clinically relevant animal model. Methods and Results: Twenty-one pigs were randomized to control, candesartan (CAN) and candesartan plus pioglitazone (CAN+PIO) groups. Drugs were administered orally for 7 days before SES implantation until the time of death. Forty-two SES were used in porcine coronary arteries. Early inflammatory cell adhesion in SES evaluated on scanning electron microscopy at 3 days was significantly suppressed in the CAN and CAN+PIO groups compared with controls. Bradykinin-induced endothelium-dependent relaxation at an adjacent segment distal to the SES evaluated using organ chambers was reduced compared with intact segments in control coronaries at 28 days. Endothelial dysfunction was reversed by CAN and even more obviously improved in the CAN+PIO group. Conclusions: Candesartan protected against vascular inflammation and restored endothelial function after SES implantation. The combination of candesartan and pioglitazone was more effective than candesartan monotherapy and might confer vascular protection when administered before SES implantation.