Synergistic Effects of Calcium-Channel and Angiotensin-Receptor Blockers on Endothelial Function and Inflammatory Responses in a Porcine Drug-Eluting Stent Model

Background: The rate of stent thrombosis is increased in association with drug-eluting stents (DES) due to delayed endothelialization and prolonged inflammation. Clinical studies have shown that either an angiotensin-receptor blocker (ARB) or a calcium-channel blocker (CCB) can improve endothelial dysfunction and inhibit inflammatory reactions in patients with hypertension. The effects of co-administered CCB and ARB on vascular protection after DES implantation, however, remain unknown. Methods and Results: Pigs (n=24) were implanted with coronary stents and randomly assigned to control, CCB, ARB or CCB + ARB groups. Endothelium-mediated vasodilation at the distal edge was significantly impaired compared to the intact site in the control group (P<0.05), but the difference between two sites in the CCB + ARB group was not significant. The combination produced a synergistic effect at the distal edge compared to the ARB, CCB and control groups (P<0.05). The expression of tumor necrosis factor-α and inflammatory cell adhesion were significantly inhibited in the CCB or ARB monotherapy groups compared with the control (P<0.05). The combination of CCB + ARB also improved inflammation. Conclusions: Implanted DES exert adverse effects such as endothelial dysfunction and inflammatory reactions. The administration of either a CCB or an ARB reversed this adverse effect. Furthermore, recovery was synergistically enhanced by a CCB combined with an ARB.  (Circ J 2010; 74: 1704 - 1710)