Local vascular dysfunction after coronary paclitaxel-eluting stent implantation

Abstract

Background

Paclitaxel-eluting stents (PES) have been shown to reduce the rate of restenosis and the need for repeated revascularization procedures compared with bare metal stents. However, long-term effects of paclitaxel on vascular function are unknown. The purpose of the present study was to assess coronary vasomotor response to exercise after paclitaxel-eluting stent implantation.

Methods

Coronary vasomotion was evaluated by biplane quantitative coronary angiography at rest and during supine bicycle exercise in 27 patients with coronary artery disease. Twelve patients were treated with a bare metal stent (controls), and fifteen patients with a paclitaxel-eluting stent. All patients were restudied 6 ± 2 (range 2–12) months after stent implantation. Minimal luminal diameter, stent diameter, proximal, distal and a reference vessel diameter were determined.

Results

Reference vessels showed exercise-induced vasodilation in both groups (+ 20 ± 5% controls; + 26 ± 3% PES group). Vasomotion within the stented vessel segments was abolished. In the controls, the adjacent segments proximal and distal to the stent showed exercise-induced vasodilation (+ 17 ± 3% and + 24 ± 4%). In contrast, there was exercise-induced vasoconstriction of the proximal and distal vessel segments adjacent to the paclitaxel-eluting stent (− 13 ± 6% and − 18 ± 4%; p < 0.005). After sublingual nitroglycerin, the proximal and distal vessel segments dilated in both groups. Exercise-induced vasoconstriction adjacent to paclitaxel-eluting stent correlated inversely with the time interval after stent implantation.

Conclusions

Paclitaxel-eluting stent implantation is associated with exercise-induced vasoconstriction in the peristent region suggesting endothelial dysfunction as the underlying mechanism. Improvement of vascular function occurs over time, indicating delayed vascular healing.

Introduction

Paclitaxel is an anti-microtubule agent interfering with neointimal vascular smooth muscle cell accumulation and proliferation [1]. For this reason, it has been considered for intracoronary delivery to arrest neointimal hyperplasia after coronary stent implantation. Several studies have shown that paclitaxel-eluting stents (PES) are effective in reducing restenosis after coronary stenting [2], [3], [4], [5], [6], [7]. Thus, drug-eluting stents, including paclitaxel- and sirolimus-eluting stents, have led to a breakthrough in the percutaneous treatment of coronary artery disease.

Despite these favorable results, concerns have been raised that drug-eluting stents may have similar potential risks as brachytherapy, such as late stent thrombosis [8], peristent restenosis [9], [10], incomplete stent apposition [11], and aneurysm formation. Comparable to brachytherapy, drug-eluting stents exert an antiproliferative effect on endothelial and vascular smooth muscle cells [12], [13]. With paclitaxel, direct inhibition of re-endothelialization has been described by Farb and coworkers [14]. Moreover, atherectomy specimens from late in-stent restenotic lesions after implantation of a paclitaxel-eluting stent have demonstrated delayed endothelial healing and chronic inflammation [15].

We have previously shown that coronary vasomotion of the peristent region is impaired after sirolimus-eluting stent implantation [16]. Similarly, Hofma demonstrated endothelial dysfunction in the peristent region after sirolimus-eluting stent implantation with acetylcholine testing [17]. Long-term results of paclitaxel-eluting stent implantation with regard to vascular integrity and coronary endothelial function are missing. Thus, the purpose of the present study was to assess coronary vascular function at different time points ranging between 2 to 12 months after paclitaxel-eluting stent implantation, using bicycle exercise as physiological stimulus for studying coronary vasomotor response.