CLINICAL RESEARCH: INTERVENTIONAL CARDIOLOGY
Differential Effects of Drug-Eluting Stents on Local Endothelium-Dependent Coronary Vasomotion
Michalis I. Hamilos, MD*,
Miodrag Ostojic, MD, PhD ,
Branko Beleslin, MD, PhD,
Dragan Sagic, MD, PhD ,
Ljubco Mangovski, MD,
Sinisa Stojkovic, MD, PhD,
Milan Nedeljkovic, MD, PhD,
Dejan Orlic, MD,
Bratislav Milosavljevic, MD,
Dragan Topic, MD,
Nevena Karanovic, MD, PhD ,
William Wijns, MD, PhD*,* on behalf of the NOBORI CORE Investigators
* Cardiovascular Centre, Aalst, Belgium
Department of Cardiology, University Institute for Cardiovascular Diseases, Clinical Center of Serbia, Belgrade, Serbia
Institute for Cardiovascular Disease Dedinje, Belgrade, Serbia
Ministry of Health of Serbia, Belgrade, Serbia.
Manuscript received October 8, 2007;
revised manuscript received November 20, 2007,
accepted December 8, 2007.
* Reprint requests and correspondence: Dr. William Wijns, Cardiovascular Center Aalst, OLV Clinic, Moorselbaan, 164, B-9300 Aalst, Belgium. (Email: William.Wijns{at}village.uunet.be).
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Abstract
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Objectives: The aim of our study was to compare coronary vasomotion after implantation of a second-generation biolimus A9-eluting stent (BES) and of a sirolimus-eluting stent (SES).
Background: Drug-eluting stents (DES) have been associated with impaired local coronary vasomotion, delayed endothelialization, and increased late thrombotic risk. New DES with different drugs, pharmacokinetics, and polymers have been developed.
Methods: Nineteen patients with a BES and 15 patients with a SES were studied 9 months after stent implantation. Endothelium-dependent and -independent coronary vasomotion were tested proximally and distally to the stent as well as at a reference segment during right atrial pacing at increasing heart rates. Quantitative coronary angiographic measurements were performed offline.
Results: Of the patients with BES, 2 showed vasoconstriction with increased heart rate and 17 showed vasodilatation. Of the patients with a SES, 9 showed vasoconstriction while 6 showed vasodilatation. The SES showed significant vasoconstriction at both the proximal (–2.3 ± 10% vs. 7.9 ± 10%) and the distal (–5.4 ± 9% vs. 6.1 ± 8%) segments to the stent compared with the BES (p = 0.003 for proximal, p < 0.001 for distal segment). Endothelium-independent vasomotion after intracoronary nitrates did not differ significantly between the 2 groups (p = NS for proximal and distal segment).
Conclusions: Unlike the case with the SES, endothelium-dependent vasomotion at adjacent stent segments seems to be preserved after BES implantation. This result may be explained by the different drug release kinetics, DES design, or characteristics of polymer used in the stent system.
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Abbreviations and Acronyms
| | BES = biolimus A9-eluting stent(s) | | DES = drug-eluting stent(s) | | PES = paclitaxel-eluting stent(s) | | QCA = quantitative coronary angiography | | SES = sirolimus-eluting stent(s) |
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Drug-eluting stents (DES) are considered a breakthrough in the treatment of coronary artery disease because of their ability to reduce rates of early restenosis and subsequent need for target lesion reintervention. However, delayed healing has been associated with an increased risk of late and very late stent thrombosis (1–3). Moreover, paradoxical coronary vasoconstriction at coronary segments adjacent to the stent has been reported for both sirolimus-eluting stents (SES) and paclitaxel-eluting stents (PES) up to 12 months after implantation (4–7). This observation may be attributable to delayed endothelialization caused by the drug and/or endothelial dysfunction caused by polymer-induced inflammation or hypersensitivity reaction. New DES have been developed with different stent designs, drugs, and polymers. Nobori (Terumo Corporation, Tokyo, Japan) is one such second-generation DES that uses a bioresorbable polymer (polylactic acid) from which biolimus A9, an analogue of sirolimus, is eluted.
The aim of our study was to asses the endothelium-dependent and -independent coronary vasomotion 9 months after either biolimus A9-eluting stent (BES) or SES implantation, using right atrial pacing at increasing rate steps. Cardiac pacing increases myocardial oxygen requirements to be matched by augmented coronary blood flow. The resulting increase in shear stress dilates human coronary epicardial arteries in the presence of functional endothelium. Endothelial cell dysfunction and the subsequent reduced nitric oxide activity are associated with paradoxical constriction of epicardial arteries with cardiac pacing (8–11).
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Methods
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Patients with BES (n = 24) and with SES (n = 19) having lesions treated with a single stent and who consented to the study protocol were included in the study. All of them underwent follow-up coronary angiography 9 ± 1 months after stent implantation as a part of the NOBORI CORE study. The NOBORI CORE study is a prospective, multicenter, comparative study of Nobori and Cypher DES systems in which all patients were scheduled to undergo angiographic follow-up. The primary end point was angiographic in-stent late loss at 9 months post-procedure. The main secondary end points were major cardiac adverse event rate at 1 and 9 months and yearly up to 5 years as well as assessment of endothelial function by atrial pacing at 9 months. The NOBORI CORE study was conducted in 5 study sites, but endothelial function assessment was planned in only 2 sites enrolling the largest number of patients. All patients consented to undergo the study protocol, which was approved by the local ethics committee.
All stents were implanted in de novo lesions. Two patients (1 in the BES and 1 in the SES group) with angiographically significant in-stent restenosis were excluded from the study protocol. In 2 patients from each group the quality of angiography was not sufficient to allow accurate measurement of vessel diameter changes, and those patients were also excluded. Finally, excluded from the analysis were patients having constriction of the reference vessel (2 in the BES group and 1 in the SES group).
Study protocol.
All vasoactive drugs were discontinued at least 24 h before catheterization except for sublingual nitroglycerin, which was withheld for at least 1 h. Long-acting beta-blockers were stopped 48 h before study.
Diagnostic left heart catheterization and coronary arteriography were performed by a standard percutaneous femoral approach. A 6-F diagnostic catheter was introduced into the left main or right coronary artery, depending on the vessel studied. A 5-F bipolar pacing wire (St. Jude Medical, St. Paul, Minnesota) was placed against the high lateral right atrial wall. The pacing study was then performed. After control conditions were established, rapid atrial pacing was conducted at 20 beats/min above baseline heart rate for 2 min, followed by increments in the pacing rate of 20 beats/min for 2 min each until a final pacing rate of 150 beats/min was reached, angina was produced, or atrioventricular Wenckebach block developed. After rapid atrial pacing, a 2-min recovery period was allowed. Intracoronary nitroglycerin (200 µg total dose) was administered. Atrioventricular Wenckebach block was not treated with intravenous atropine in order not to influence coronary vasomotion and blood flow responses. Pacing from the right ventricle was performed up to 150 beats/min in the patients in whom atrioventricular Wenckebach block developed at rates below 110 beats/min.
Serial contrast injections of the study vessel were performed at baseline, at the end of a 2-min period at each pacing rate, immediately after ending the pacing, and after intracoronary nitroglycerin administration. Heart rate and blood pressure were digitally recorded during the entire study protocol.
Quantitative coronary angiography.
Coronary angiography was performed on a digital X-ray system (Axiomatis dSC, Siemens Medical Solutions, Malvern, Pennsylvania) at 25 frames/s. An appropriate view that permitted clear visualization of both the target artery and the reference vessel segment was selected. The angle of the view, the distance from the X-ray focus to the object, and the distance from the object to the image intensifier were kept constant during the study.
The computer-based ACOM.PC 5.01 (Siemens Medical Solutions) was used for off-line quantitative coronary angiography (QCA) analysis. All measurements were done by an independent observer who was blinded to the study protocol and type of stent implanted. Percent changes were calculated in all patients using the baseline angiogram as reference. In both groups, a reference angiographically normal segment in another vessel not related to the stented lesion as well as the stented segment and its adjacent segments proximal and distal were assessed (at least 5 mm up to 15 mm proximal and distal to the stent edges). If the intervened vessel was the right coronary artery, an angiographically normal segment as far as possible from the stented vessel segment was taken as reference. Because of stent placement in an ostial vessel segment, the proximal segments could not be evaluated in 4 patients in the BES group and in 2 patients in the SES group. All measurements were done exactly at the same segment, at baseline, at every pacing step, immediately after stopping pacing and after intracoronary nitrates. A progressive reduction in vessel diameter was termed as vasoconstriction, and an increase as vasodilatation. Patients with vasoconstriction in the reference segment were not included in the final analysis because they were considered to have a generalized endothelial disease. Normalization of vessel diameters for the maximal vasodilated state was performed by dividing resting and pacing data by the vessel diameter after nitrates administration. In our laboratory, coronary artery diameter measurements performed with the ACOM.PC 5.01 (Siemens Medical Solutions) have interobserver variability of 0.11 mm, and intraobserver variability of 0.08 mm for mean lumen diameter on repeated analysis of the same frame.
Statistical analysis.
Statistical analysis was performed using the SAS 9.1 software (SAS Institute Inc., Cary, North Carolina). Continuous data are summarized as mean ± standard deviation. Unpaired or paired t test were adequately used to analyze differences in continuous variables. Fisher and chi-square tests were used to analyze differences between categorical variables. A general linear model was performed to adjust the vasomotor response to the baseline parameters and to predict the vasomotor response. All statistical comparisons were performed at the 5% level of significance.
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Results
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The baseline characteristics of the patients included in the analysis are comparable (Table 1). Mean time from implantation was 9.12 ± 1.0 months for SES and 9.9 ± 0.9 months for BES. In the SES group, 8 stents were implanted in the left anterior descending artery, 5 in the left circumflex artery, and 2 in the right coronary artery (numbers for BES were 10, 3, and 6, respectively; p = NS). One patient in each group required right ventricular pacing because of developing atrioventricular block at heart rate below 110 beats/min.
Hemodynamic data.
Baseline and maximal pacing rate, mean arterial pressure at baseline and at maximal pacing rate, and rate-pressure product both at baseline and at maximal pacing rate were similar in the 2 groups (Table 2). Mean arterial blood pressure did not change significantly during pacing compared with baseline in the BES group (from 95 ± 2.9 mm Hg to 95.4 ± 3.8 mm Hg, p = NS), whereas it was increased significantly in the SES group (from 96 ± 3.5 mm Hg to 101 ± 4.5 mm Hg, p = 0.011). Mean arterial pressure changes from baseline to peak pacing were not statistically significant between SES and BES (4.6 mm Hg vs. 1.0 mm Hg, p = 0.22 respectively).
Coronary vasomotor response to pacing and nitrates.
Mean data for the 2 patient groups with regard to mean vessel diameter of the proximal, stented, distal, and reference segments are shown in Table 3. For the segment proximal to the stent, normal vasomotion (vasodilatation) was maintained in the BES group, whereas vasoconstriction was observed in the SES group (7.9 ± 10% vs. –2.3 ± 10%, p = 0.003) (Figs. 1 and 2). For the segment distal to the stent, normal vasomotion (vasodilatation) was maintained in the BES group, whereas vasoconstriction was observed in the SES group (6.1 ± 8% vs. –5.4 ± 9%, p < 0.001) (Figs. 1 and 2). In the SES group, the vasomotor response in the reference segment was better than in both the proximal and the distal segments (–2.3 ± 10% for proximal and –5.4 ± 9% for distal vs. 10 ± 0.4% for reference, p < 0.001 for both). In the BES group, reference segments had a higher vasodilatory response from the distal segment (6.1 ± 8% vs. 13 ± 0.6%, p = 0.003) but not from the proximal segment (7.9 ± 10% vs. 13 ± 0.6%, p = NS). The stented vessel segments in both groups showed no diameter change (Table 3). The reference segment not related to the stented segment showed pacing-induced vasodilatation in both groups (13 ± 0.6% in BES, 10 ± 0.4% in SES, p = NS). Intracoronary nitrates were associated with maximal vasodilatation of all of the evaluated vessel segments (proximal, distal, and reference) in both groups (Table 3). The maximal vasodilatation observed after nitroglycerin administration was not statistically significantly different for any of the segments between the 2 groups.
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Table 3 Quantitative Coronary Angiography Measurements in Both Groups at Baseline, Maximal Pacing, and After Nitroglycerin Administration
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Figure 1 Distribution of Diameter Changes in Patients With BES and SES
Scatterplots showing the distribution of percent mean diameter changes from baseline to maximal pacing rate in patients with biolimus A9-eluting stents (BES) and sirolimus-eluting stents (SES), in proximal (A) and distal (B) segments.
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Figure 2 Mean Diameter of the Proximal, Distal, and Reference Segments in the BES and SES Groups
Mean diameter values at baseline, maximal pacing rate, and after nitroglycerin administration in BES and SES groups, in proximal (A), distal (B), and reference (A and B) segments. The p values for the comparison between BES and SES are indicated for both proximal and distal segments. Abbreviations as in Figure 1.
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Discussion
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Our study is the first to show that a newer-generation DES is associated with better endothelium-dependent coronary vasomotor response than SES, whereas the nonendothelium-dependent vasomotor response was preserved in all cases and did not differ significantly between the 2 groups. These findings pertain only to the 2 stents under study. Despite the similarities between biolimus and sirolimus, it is unknown whether our findings are related to stent, polymer, or to a drug class effect.
Endothelial function after stent implantation.
Implantation of balloon expandable stents is necessarily associated with vessel wall injury and trauma to the coronary endothelium. This trauma sets in motion the inflammatory reaction and healing response that eventually leads to re-endothelialization. In the first month after the implantation of a bare-metal stent, a new immature endothelial layer covers the stent struts, reestablishing a normal coronary vessel wall lining. Autopsy studies suggest that endothelium recovery is complete 3 months after the implantation, but functionality of the neo-endothelium has not been investigated (12). In a study by Maier et al. (13), coronary vasomotion after exercise testing during coronary angiography was normal in segments distal and proximal to bare-metal stent 6 months after implantation.
After implantation of SES, a more pronounced inflammatory response has been described that may occasionally be associated with a local hypersensitivity reaction and eosinophilic infiltration. The synthetic polymer containing the drug may be an important trigger of local coronary inflammation, even though the metal struts or the stent itself may participate in this reaction. Coronary inflammation is responsible for delayed re-endothelialization of stent and vessel wall, which eventually results in a delayed vascular healing response. Sirolimus impairs the normal healing processes of the injured arterial wall by inhibiting endothelial cell proliferation (14). In addition, sirolimus was shown to enhance tissue factor expression in human endothelial cells (15), and inhibits the migration and proliferation of endothelium progenitor cells, which may play an important role in endothelium regeneration (16,17). These findings suggest that SES may impair both the endothelial regeneration and the ability of endothelial cells to exert their normal function.
Poor stent endothelialization means that stent struts are in direct contact with blood and its elements. Human autopsies showed insufficient endothelial coverage and delayed arterial healing with SES, regardless of the delay from implantation (18–23). These findings are complemented by angioscopy (24) and optical coherence tomographic imaging (25), which showed incomplete endothelialization and uncovered stent struts 3 to 6 months after SES implantation. Complete or partial lack of re-endothelialization of stent struts and vessel wall generates a long-lasting, unhealed vessel wall surface favoring platelet adhesion and aggregation, which may eventually cause thrombus formation.
Endothelial recovery and vasomotor response after BES implantation.
All of those concerns led to new targets in DES development with use of bioerodable polymers and drugs specifically developed for local application. The Nobori coronary stent system uses a bioresorbable polymer (polylactic acid) from which biolimus A9 is eluted. Biolimus A9 is a new sirolimus derivative that binds to the cytosolic immunophilin FK binding protein 12. The formed complex binds to the mammalian target of rapamycin and inhibits growth factor-driven cell proliferation, including T-cells and vascular smooth muscle cells. It has the potential to prevent restenosis in coronary stents by interrupting smooth muscle cell migration and proliferation. In addition, an enhanced lipophilicity enables an increased uptake in local target tissues and reduced presence in areas surrounding the stented segment or even in the systemic circulation.
In our study, BES showed a better-preserved endothelium-dependent vasomotor response compared with SES. There are several possible explanations for this observation. Biolimus A9 is a more lipophilic drug than sirolimus, and upon release would quickly bind to the target lipid-rich tissue. Of note, drug is present only on the vessel side (abluminally), and as such enters into peripheral circulation only in minimal quantities (26). This results in a more localized effect and less systemic drug exposure. Animal studies showed that after BES implantation, the tissue concentration of the drug in segments 5 mm proximal and distal to the stent edges is almost nonmeasurable (26) and stent endothelialization is more complete than with SES and PES (27). In addition, SES and BES have different drug release kinetics: total drug content is released from the SES within 60 days with more than 60% released shortly after stent implantation (28), versus a small initial burst and sustained simultaneous drug release and polymer degradation taking place over 6 months in the BES (26), exposing the surrounding tissue at any given time to a lower amount of drug. Finally, the polymer used with BES is expected to be absorbed in a few months. Because durable polymers have been held responsible for some of the late adverse events related to SES, it is expected that the degradation of polymer will improve arterial healing and long-term safety of BES.
The fact that the majority of our patients with BES had a vasodilatory response to pacing is a robust indication that functional endothelial re-growth is almost complete 9 months after implantation. The findings of our study give some promise that newer-generation DES with different drug and polymer platforms may be more respectful of the vessel healing while remaining at least as effective (29,30).
In our study, the response of the different patients to pacing was by and large homogenous. Some patients with SES seemed to have a normal vasodilatory response to pacing, albeit blunted, whereas some patients with BES had a vasoconstrictive response. Because the time course of arterial healing after DES placement may vary from patient to patient, endothelialization was probably more complete in some patients than in others, for reasons that are not well understood. In addition, the time after stent implantation was longer than in previous studies, which may theoretically allow for further healing. The time course of recovery of endothelial function still needs to be studied systematically.
Previous studies.
To our knowledge there is no other published study that examines coronary vasomotion after implantation of a newer-generation DES. On the contrary, there are 3 published studies that all showed agreement with our findings that SES cause local coronary vasoconstriction 6 months after their implantation compared with bare metal stents (5–7). Two of those studies (5,7) used acetylcholine and the third used exercise (6) to assess coronary endothelial function.
The more pronounced vasoconstrictive response after SES implantation reported in those studies could be explained by the different time points at which coronary vasomotion was tested and the different methods used to assess vasomotion. In 2 of those studies, acetylcholine was used to test the endothelial function. Despite the fact that acetylcholine infusion has been extensively used for measuring coronary vasomotor response, we believe that flow-mediated changes induced by pacing are a more physiological stimulus than a pharmacological test for the assessment of endothelial function.
Study limitations.
Baseline endothelial function before stent implantation was not assessed in our study. The assessment of endothelial function in patients with significant coronary lesions is not practicable, first because it is difficult to stop antianginal vasoactive medication before the intervention, and second because it is not feasible to avoid the use of intracoronary nitrates during the procedure.
At the time of the intervention, stent assignment was not randomized. Patient enrollment was done in waves: all treated patients in each institution complying with inclusion criteria were treated simultaneously with BES or SES at pre-defined study periods determined by the availability of BES. Because the assignment of stent type was dependent only on the time point of study inclusion, bias with regard to stent-type decision was minimal and has probably not influenced the result.
We assessed endothelial function 9 months after both stent implantations, and accordingly our results refer to this specific time point. Further studies are needed to see whether the differences observed between the 2 stents are still present more than 9 months after their implantation. Moreover this study cannot indicate differences in the clinical outcomes after both stent implantations, although NOBORI CORE data at 9 months show equivalence of the 2 stents in terms of safety, angiographic results, and clinical efficacy (30).
Calcium channel blockers were more frequently used in the SES group. The 24-h period of interruption is long enough for a complete washout. Moreover, the fact that the SES group showed more vasoconstriction than the BES group indicates that the difference in the use of these drugs could not have influenced our results.
Finally, the clinical relevance of our findings remains unknown. Local coronary vasoconstriction is only an indirect sign of endothelial dysfunction, probably caused by delayed endothelialization in the segments proximal and distal to the stent. Delayed endothelialization in the coronary vessels has been closely related to several adverse events (31), the most severe of which is thrombus generation. Accordingly this finding could partially explain the increased late thrombotic events observed with the first-generation DES.
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Conclusions
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Endothelium-dependent vasomotion at adjacent stent segments seems to be better preserved after BES implantation than SES implantation. This finding is a strong indicator of a functionally complete endothelial regeneration, a fact that may hold promise for reducing thrombotic events with this stent platform.
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Appendix
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For a complete list of investigators, please see the online version of this article.
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Acknowledgments
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The authors thank all of the patients who agreed to participate in this study. Special thanks to the technicians and support staff in all participating hospitals.
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Footnotes
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Dr. Hamilos is supported by a Hellenic Society of Cardiology fellowship.
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References
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1. Camenzind E, Steg PG, Wijns W. Stent thrombosis late after implantation of first-generation drug-eluting stents: a cause for concern Circulation 2007;115:1440-1455.[Free Full Text]2. Stone GW, Moses JW, Ellis SG, et al. Safety and efficacy of sirolimus- and paclitaxel-eluting coronary stents N Engl J Med 2007;356:998-1008.[Abstract/Free Full Text] 3. Lagerqvist B, James SK, Stenestrand U, SCAAR Study Group Long-term outcomes with drug-eluting stents versus bare-metal stents in Sweden N Engl J Med 2007;356:1009-1019.[Abstract/Free Full Text] 4. Togni M, Raber L, Cocchia R, et al. Local vascular dysfunction after coronary paclitaxel-eluting stent implantation Int J Cardiol 2007;120:212-220.[CrossRef][Web of Science][Medline] 5. Hofma S, Van der Giessen W, Van Dalen B, et al. Indication of long-term endothelial dysfunction after sirolimus-eluting stent implantation Eur Heart J 2006;27:166-170.[Abstract/Free Full Text] 6. Togni M, Windecker S, Cocchia R, et al. Sirolimus-eluting stents associated with paradoxic coronary vasoconstriction J Am Coll Cardiol 2005;46:231-236.[Abstract/Free Full Text] 7. Fuke S, Maekawa K, Kawamoto K, et al. Impaired endothelial vasomotor function after sirolimus-eluting stent implantation Circ J 2007;71:220-225.[CrossRef][Web of Science][Medline] 8. Nabel EG, Selwyn AP, Ganz P. Paradoxical narrowing of atherosclerotic coronary arteries induced by increases in heart rate Circulation 1990;81:850-859.[Abstract/Free Full Text] 9. Prasad A, Husain S, Quyyumi A. Abnormal flow-mediated epicardial vasomotion in human coronary arteries is improved by angiotensin-converting enzyme inhibition. A potential role of bradykinin. J Am Coll Cardiol 1999;33:796-804.[Abstract/Free Full Text] 10. Hanet C, Schroeder E, Michel X, et al. Flow-induced vasomotor response to tachycardia of the human internal mammary artery and saphenous vein grafts late following bypass surgery Circulation 1991;84Suppl:III268–74. 11. Hanet C, Evrard P, Jacquet L, Goenen M, Robert A. Flow-mediated vasodilator response to tachycardia of epicardial coronary arteries is preserved in heart transplant recipients Circulation 1993;88:II257-II262.[Medline] 12. Grewe PH, Deneke T, Machraoui A, Barmeyer J, Muller KM. Acute and chronic tissue response to coronary stent implantation: pathologic findings in human specimen J Am Coll Cardiol 2006;35:157-163.[CrossRef] 13. Maier W, Windecker S, Küng A, et al. Exercise-induced coronary artery vasodilation is not impaired by stent placement Circulation 2002;105:2373-2377.[Abstract/Free Full Text] 14. Parry TJ, Brosius R, Thyagarajan R, et al. Drug-eluting stents: sirolimus and paclitaxel differentially affect cultured cells and injured arteries Eur J Pharmacol 2005;524:19-29.[CrossRef][Web of Science][Medline] 15. Steffel J, Latini RA, Akhmedov A, et al. Rapamycin, but not FK-506, increases endothelial tissue factor expression: implications for drug-eluting stent design Circulation 2005;112:2002-2011.[Abstract/Free Full Text] 16. Fukuda D, Sata M, Tanaka K, Nagai R. Potent inhibitory effect of sirolimus on circulating vascular progenitor cells Circulation 2005;111:926-931.[Abstract/Free Full Text] 17. Inoue T, Sata M, Hikichi Y, et al. Mobilization of CD34-positive bone marrow-derived cells after coronary stent implantation: impact on restenosis Circulation 2007;115:553-561.[Abstract/Free Full Text] 18. Finn AV, Kolodgie FD, Harnek J, et al. Differential response of delayed healing and persistent inflammation at sites of overlapping sirolimus- or paclitaxel-eluting stents Circulation 2005;112:270-278.[Abstract/Free Full Text] 19. Finn AV, Nakazawa G, Joner M, et al. Vascular responses to drug-eluting stents: importance of delayed healing Arterioscler Thromb Vasc Biol 2007;27:1500-1510.[Abstract/Free Full Text] 20. Finn AV, Joner M, Nakazawa G, et al. Pathological correlates of late drug-eluting stent thrombosis. Strut coverage as a marker of endothelialization. Circulation 2007;115:2435-2441.[Abstract/Free Full Text] 21. Virmani R, Guagliumi G, Farb A, et al. Localized hypersensitivity and late coronary thrombosis secondary to a sirolimus-eluting stent: should we be cautious? Circulation 2004;109:701-705.[Abstract/Free Full Text] 22. Joner M, Finn A, Farb A, et al. Pathology of drug-eluting stents in humans. Delayed healing and late thrombotic risk. J Am Coll Cardiol 2006;48:193-202.[Abstract/Free Full Text] 23. Luscher TF, Steffel J, Eberli FR, et al. Drug-eluting stent and coronary thrombosis: biological mechanisms and clinical implications Circulation 2007;115:1051-1058.[Abstract/Free Full Text] 24. Kotani J, Awata M, Nanto S, et al. Incomplete neointimal coverage of sirolimus-eluting stents: angioscopic findings J Am Coll Cardiol 2006;47:2108-2111.[Abstract/Free Full Text] 25. Matsumoto D, Shite J, Shinke T, et al. Neointimal coverage of sirolimus-eluting stents at 6-month follow-up: evaluated by optical coherence tomography Eur Heart J 2007;28:961-967.[Abstract/Free Full Text] 26. Ostojic M. Nobori Pharmacokinetics studyhttp://www.europcronline.com/fo/lecture 2007Accessed November 19, 2007. 27. Virmani R. Coronary drug-eluting stents: from animal studies to clinical practicehttp://www.europcronline.com/fo/lecture 2007Accessed November 19, 2007. 28. Vetrovec G, Rizik D, Williard C, et al. Sirolimus PK trial: a pharmacokinetic study of the sirolimus-eluting Bx velocity stent in patients with de novo coronary lesions Catheter Cardiovasc Interv 2006;67:32-37.[CrossRef][Web of Science][Medline] 29. Chevalier B, Serruys PW, Silber S, et al. Randomized comparison of Nobori, Biolimus A9-eluting coronary stent with a Taxus, paclitaxel-eluting coronary stent in patients with stenosis in native coronary arteries: The Nobori 1 trial Eurointerv 2007;2:426-434. 30. Ostojic M, Sagic D, Beleslin B, et al. First clinical comparison of Nobori-Biolimus A9 drug eluting stent with Cypher-Sirolimus eluting stent: NOBORI CORE nine months and one year clinical outcomes Eurointerv 2008;3:574-579. 31. Schachinger V, Britten MB, Zeiher AM. Prognostic impact of coronary vasodilator dysfunction on adverse long-term outcome of coronary heart disease Circulation 2000;101:1899-1906.[Abstract/Free Full Text]
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Abstract
Methods