Local vascular dysfunction after coronary paclitaxel-eluting stent implantation
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.
Section snippets
Methods
Thirty-one patients were invited to undergo repeat coronary angiography after bare metal stent (BMS) or paclitaxel-eluting stent (PES) implantation. Three patients with a bare metal stent and one patient with a paclitaxel-eluting stent had to be excluded because of the development of in-stent restenosis. Finally, twelve patients with successful bare metal stent implantation (control group) and fifteen patients with slow-release, paclitaxel-eluting stent (TAXUS™, Boston Scientific, Natick, MA)
Results
A representative coronary angiogram is shown at rest and during bicycle exercise in a patient three months after implantation of two paclitaxel-eluting stents in series into the left circumflex artery (Fig. 1). This patient developed chest pain during exercise. Baseline coronary angiography revealed patent stents. The proximal and distal vessel segments adjacent to both stents (= peristent region) showed severe coronary vasoconstriction during dynamic exercise. This vasoconstrictory response was
Discussion
Drug-eluting stents are effective at decreasing rates of angiographic restenosis and major adverse cardiac events compared with bare metal stents [19]. However, several issues have been associated with the use of drug-eluting stents, namely late stent thrombosis [8], hypersensitivity reactions to the polymer-coating [20], incomplete stent apposition and aneurysm formation [11], delayed healing with lack of re-endothelialization [14], [15], edge restenosis (peristent lesions) [9], and abnormal
Limitations
The assessment of endothelial function in human coronary arteries is based on changes in coronary flow and dimensions induced by the infusion of vasoactive substances or by physical exercise. In the present study, exercise was used as a physiologic stimulus for evaluation of endothelial function. Since this technique requires not only experienced and trained personnel for exercise coronary angiography, but also the cooperation of the patient, case numbers are usually small and limited to mildly
Conclusions
Coronary artery stenoses show exercise-induced vasoconstriction, whereas normal vessels dilate. Bare metal stent placement abolishes paradoxical vasoconstriction of the coronary arteries and does not adversely affect vasomotion of the adjacent vessel segments. In the present study, we observed paradoxical vasoconstriction during exercise in vessel segments adjacent to paclitaxel-eluting stents although dilatatory response to nitroglycerin was maintained. These findings are similar to those
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2020, JACC: Basic to Translational ScienceCitation Excerpt :NO production is impaired in damaged endothelium after angioplasty and is responsible for de novo and in-stent restenosis (29,30). Stents eluting antiproliferative agents such as sirolimus and paclitaxel are more deleterious than bare-metal stents in impairing endothelium-dependent relaxation responses to acetylcholine, reducing endothelial NO synthase expression and local NO production (31,32). These effects lead to a failure of re-endothelialization and vascular repair, and they account for the high rates of very late stent thrombosis in association with drug-eluting stent implantation (5).
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