Interference of Drug-Eluting Stents With Endothelium-Dependent Coronary Vasomotion

Abstract

Background-There is evidence that endothelial coverage of drug-eluting stents might be delayed or absent, a risk factor for late thrombotic events. We studied the effects of different drug-polymer-device iterations on endothelium-dependent coronary vasomotion. Systemic markers of endothelial inflammation were correlated with coronary vasomotor changes. Methods and Results-Patients with paclitaxel-eluting stents (nϭ11), sirolimus-eluting stents (nϭ21), biolimus A9-eluting stents (nϭ28), zotarolimus-eluting stents (nϭ10), and bare-metal stents (nϭ13) were studied 10, 9, 9, 9, and 12 months after implantation, respectively. Endothelium-dependent coronary vasomotion was tested proximally and distally to the stent and at a reference vessel segment during atrial pacing at increasing heart rates by quantitative coronary angiography. Indexes of platelet-monocyte binding and other biomarkers were studied in a subgroup of 19 patients. The baseline characteristics and hemodynamics of the patients in the different stent groups were comparable. Significant differences were observed across the 5 stent groups, concerning the vasomotion of segments proximal (Pϭ0.006) and distal (Pϭ0.003) to the stent. Normal vasomotion (vasodilatation) was maintained in the biolimus A9-eluting stent, zotarolimus-eluting stent, and bare-metal stent groups, whereas vasoconstriction was observed in the sirolimus-eluting stent and paclitaxel-eluting stent groups. Platelet-monocyte binding in whole blood showed a significant inverse correlation with vasomotion in reference but not in segments adjacent to the stent (rϭϪ0.57; Pϭ0.01). Conclusions-Paclitaxel-eluting stents and sirolimus-eluting stents seem to cause endothelial dysfunction of the implanted vessel, whereas biolimus A9-eluting stents and zotarolimus-eluting stents behave more closely to bare-metal stents, with preserved endothelial vasomotor response. Coronary vasoconstriction was not associated with detectable systemic endothelial activation.

Guidelines for Diagnosis and Treatment of Patients With Vasospastic Angina (Coronary Spastic Angina) (JCS 2013)

“…However, exercise and pacinginduced vasoconstriction was observed at the edges of DES and segments distal to DES. 286, 287 It has been reported that vasoconstriction in segments adjacent to stents in response to intracoronary acetylcholine infusion is more severe in DEStreated vessels than in BMS-treated vessels. 288,289 Recent studies in a porcine model and in patients with coronary artery disease have suggested that Rho-kinase, a molecular switch that regulates vascular smooth muscle contraction, plays an important role in the pathogenesis of coronary dysfunction after DES implantation, and that DES induces smooth muscle dysfunction as well as endothelial dysfunction.…”

Coronary Endothelial Dysfunction after Drug-Eluting Stent Implantation

“…Their study revealed that SES and PES showed vasoconstriction, while on the other hand, ZES and BES had vasodilatory responses that were similar to BMS (Hamilos et al, 2008b).…”

“…Comparison of first generation and second generation DES: Hamilos et al (2008b) evaluated the influence of BMS and four types of DES on endothelium-dependent vasodilation. Their study revealed that SES and PES showed vasoconstriction, while on the other hand, ZES and BES had vasodilatory responses that were similar to BMS (Hamilos et al, 2008b).…”

Involvement of Rho-Kinase Activation in the Pathogenesis of Coronary Hyperconstricting Responses Induced by Drug-Eluting Stents in Patients With Coronary Artery Disease

“…38 The recent studies demonstrated that coronary vasomotion was preserved with a new-generation biolimus-eluting stent with bioresorbable polymers as compared with the Cypher stent. 39, 40 Since we are examining the Rho-kinase activation with a new generation of DES, we would like to report our findings separately in the future. However, it also should be emphasized that Cypher TM has already been deployed in millions of patients worldwide, and thus, aggressive efforts should be made to improve coronary vasomotion in those patients implanted with Cypher TM .…”