This Article Abstract Figures Only Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Services Email this article to a friend Similar articles in this journal Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Costa, J. R. Articles by Sousa, J. E. Search for Related Content PubMed Articles by Costa, J. R., Jr Articles by Sousa, J. E.

Preliminary Results of the Hydroxyapatite Nonpolymer-Based Sirolimus-Eluting Stent for the Treatment of Single De Novo Coronary Lesions

A First-in-Human Analysis of a Third-Generation Drug-Eluting Stent System

J. Ribamar Costa, Jr, MD^_*, Alexandre Abizaid, MD, PhD^_*,_*, Ricardo Costa, MD^_*, Fausto Feres, MD, PhD^_*, Luís Fernando Tanajura, MD, PhD^_*, Andréa Abizaid, MD, PhD^_*, Luiz Alberto Mattos, MD, PhD^_*, Rodolfo Staico, MD^_*, Dimytri Siqueira, MD^_*, Amanda G.M.R. Sousa, MD, PhD^_*, Raoul Bonan, MD, J. Eduardo Sousa, MD, PhD^_*

^_* Instituto Dante Pazzanese de Cardiologia, São Paulo, Brazil
Montreal Heart Institute, Montreal, Quebec, Canada

	Abstract

Top Abstract Methods Results Discussion Conclusions REFERENCES

 
Objectives: We sought to investigate the performance and efficacy of the third-generation polymer-free Vestasync-eluting stent (VES).

Background: Recent concerns regarding the long-term safety of drug-eluting stents have been raised. Synthetic polymers have been associated with intensive inflammatory response and late stent thrombosis. Newly developed, the VES combines a stainless steel platform with a nanothin-microporous hydroxyapatite surface coating impregnated with a polymer-free sirolimus formulation (55 µm).

Methods: In May 2007, 15 patients with single de novo lesion located in native coronary arteries 3.0 to 3.5 mm in diameter and 14 mm in length were consecutively enrolled. Primary end points included in-stent late lumen loss and in-stent percent of obstruction at 4 months. Serial angiography and intravascular ultrasound were obtained at the index procedure and repeated at 4-month follow-up.

Results: Mean population age was 63.8 years; 33% of patients were diabetic. The left anterior descending artery was the prevalent target vessel (47%). Reference vessel diameter and lesion length were 2.67 ± 0.32 mm and 9.98 ± 1.98 mm, respectively. The VES was successfully implanted in all cases, and there were no procedure and in-hospital complications. Life-long aspirin and 6-month clopidogrel therapy were prescribed for all patients. At 4 months, in-stent late lumen loss was 0.30 ± 0.25 mm and percent of stent obstruction was 2.8 ± 2.2%. After up to 6 months of clinical follow-up, no major adverse cardiac event was registered.

Conclusions: The third-generation VES demonstrated excellent acute results in the treatment of de novo coronary lesions. Longer follow-up with a more complex subset of patients and lesions is required to confirm these preliminary results.

Key Words: drug-eluting stents • Vestasync • hydroxyapatite

Abbreviations and Acronyms   CK = creatine kinase   CK-MB = creatine kinase-myocardial band   DES = drug-eluting stent   IVUS = intravascular ultrasound   QCA = quantitative coronary angiography   VES = Vestasync-eluting stent

The synthetic polymer, an essential component of these first-generation devices, has been associated with an intensive inflammatory response (6). Animal histopathology and ex-vivo model analysis have shown exacerbated positive vessel remodeling, possibly caused by local response to the polymer presence (7). Importantly, the association between exacerbated vessel enlargement and very late DES thrombosis has been recently demonstrated (8,9).

As a consequence, there is a major interest in developing new DES with greater flexibility, radiopacity, and better safety profile. Recently developed, the Vestasync-eluting stent (VES) (MIV Therapeutics, Inc., Atlanta, Georgia) combines a stainless steel platform with a nanothin-microporous hydroxyapatite surface coating impregnated with a polymer-free sirolimus formulation (55 µg).

After positive preclinical studies, this first-in-human investigation was conceived to evaluate to investigate the safety, performance, and efficacy of this third-generation polymer-free DES.

	Methods

Top Abstract Methods Results Discussion Conclusions REFERENCES

 
Study population.   In May 2007, a consecutive cohort of patients with single, de novo lesions <14 mm in length, located at native coronaries of diameters from 3.0 to 3.5 mm (by visual assessment) were consecutively enrolled in this first-in-human study. Patients should present symptoms of angina (stable/unstable) or silent ischemia clearly documented through noninvasive assessment. Patients treated within 72 h of an acute myocardial infarction and/or requiring more than 1 stent to treat the target lesion were excluded from this study. We also excluded patients who had heavily calcified lesions, lesions at bifurcations or involving the ostium of the coronary vessel, severe left ventricular dysfunction (left ventricular fraction <30%), visible thrombus, and contraindications to any of the protocol medications.

The protocol was approved by the local Ethics Committee, and written informed consent was obtained from all patients before inclusion in the study.

Device description.   As with most DES systems, the Vestasync hydroxyapatite nonpolymer-based sirolimus-eluting stent system comprises 3 basic components: a platform, an antiproliferative agent, and a drug carrier. In the following text, we briefly describe all 3 components used in this novel device.

Stent platform.   The GenX stainless steel (316 L) coronary artery stent (MIV Therapeutics, Inc.) is the new-generation variable geometry stent designed to minimize stent-induced arterial injury (strut thickness = 105 µm). The GenX stent is pre-mounted on a polyamide balloon catheter between 2 platinum iridium radio-opaque markers bands, nominally 0.5 mm longer than the stent. Mounted stent length and location are defined by radio-opaque marker.

Nonpolymeric drug carrier.   The coating is composed of a microporous hydroxyapatite [Ca10(PO4)6(OH)2] underlying coating. Sirolimus in a biocompatible oil-based formulation is loaded into the microporous hydroxyapatite coating.

Hydroxyapatite constitutes 70% of natural bone composition and therefore posseses excellent biocompatibility. It does not invoke an inflammatory reaction or foreign body response and is therefore meant to improve the biocompatibility of metallic implants (10). Studies regarding the safety of hydroxyapatite implants have shown no evidence of toxicity. Long-term clinical data have shown the biocompatibility and safety of hydroxyapatite coatings in clinical settings (10–14). Furthermore, Pezzantini et al. (14) have shown that in the presence of hydroxyapatite nanocrystals, endothelial cells maintain morphological and biochemical markers of a healthy functioning endothelium, without the acquisition of proinflammatory phenotypes (14).

The hydroxyapatite coating thickness is on the order of 500 to 700 nm and possesses porosity in the range of 100 to 500 nm in diameter. The oil-based carrier of sirolimus uniformly fills the porosity of the hydroxyapatite coating without adding to the thickness of the coating; therefore, the final drug delivery coating remains under 1 µm in thickness. Figure 1 shows the scanning electron micrograph pictures of the hydroxyapatite coating as well as the final coating system. Because of the minimal coating thickness, the amount of the carrier material for the drug is significantly minimized.

View larger version (163K): [in this window] [in a new window] [Download PPT slide]   Figure 1 Main Components of the Vestasync Sirolimus-Eluting Stent System Scanning electron micrographs of (A) microporous hydroxyapatite coating, (B) cross section of the hydroxyapatite coating, (C) final coating, including the hydroxyapatite filled with sirolimus formulation, and (D) cross section of the final coating.

Antiproliferative agent sirolimus.   Sirolimus (Rapamune), a natural macrocyclic lactone, is a potent immunosuppressive agent that was developed by Wyeth-Ayerst Laboratories (Madison, New Jersey) and approved by the Food and Drug Administration (FDA) for the prophylaxis of renal transplant rejection in 1999 (15). Sirolimus binds to an intracellular receptor protein and elevates p27 levels, which leads to the inhibition of cyclin/cyclin-dependent kinase complexes and, ultimately, induces cell-cycle arrest in the late G1 phase. It inhibits the proliferation of both rat and human smooth muscle cells in vitro (16,17) and reduces intimal thickening in models of vascular injury (18–20).

Regarding sirolimus kinetics in the VES, in vitro testing on crimped and expanded stents at 37°C in 7.4 pH buffered saline demonstrates a drug release rate (in micrograms per time point, not percentage of loaded drug) that is almost the same as that of the Cypher stent for the first hour. Thereafter, the release rate slows down to less than half the rate of Cypher. By in vitro experimentation, it is calculated that 100% of the drug will be released from the stent in approximately 3 to 4 weeks.

Procedure.   For the present study, the VES was available in only 2 diameters (3.0 and 3.5 mm) and a single length (19 mm). The eluted dose of sirolimus was less than half of the dose used in the Cypher stent (55 µg vs. 140 µg).

All interventions were performed according to the current standard guidelines. After mandatory predilation of the target lesion, stents were deployed with high pressure after dilation.

Dual antiplatelet therapy including loading dose of aspirin (200 to 325 mg) and thienopyridine (clopidogrel 300 mg) was started at least 24 h before the procedure. Post-procedural aspirin was continued indefinitely, and clopidogrel was maintained for 6 months (75 mg/day). During the procedure, intravenous heparin (70 to 100 IU/kg) was administered after sheath insertion to maintain an activated clotting time >250 s. Use of additional medications during the procedure, including glycoprotein IIb/IIIa inhibitors, was left to the operator's discretion.

A 12-lead electrocardiogram was obtained: 1) before the procedure; 2) immediately afterward; and 3) 24 h later. Blood sample laboratory analysis included cardiac enzymes creatine kinase (CK) and creatine kinase-myocardial band (CK-MB) before the procedure (<24 h) and 12 to 18 h after treatment.

Follow-up.   After discharge, patients were clinically followed up by medical appointments at 1, 3, and 6 months. Additional clinical follow-up at 9, 12, and 24 months is expected by protocol. Angiography and intravascular ultrasound (IVUS) follow-up was scheduled for 4 months after the baseline procedure.

Quantitative coronary angiography (QCA) analysis.   Angiographic studies were performed at baseline, after the procedure, and at follow-up, in 2 orthogonal views, after the intracoronary administration of 100 to 200 µg nitroglycerin. The same angiographic angles performed at baseline were reproduced at the subsequent studies. Digital angiograms were analyzed off line with the use of an automated edge-detection system (QCA-CMS, Medis Medical Imaging Systems, Nuenen, the Netherlands). Lesion morphology was assessed by using standard criteria, and lesion complexity was defined according to the modified American College of Cardiology/American Heart Association (ACC/AHA) classification system (21). The contrast-filled catheter tip was used for calibration.

Quantitative angiographic parameters included: 1) reference vessel diameter; 2) minimum lumen diameter; 3) lesion length; 4) percent diameter stenosis (difference between the reference diameter and minimum lumen diameter divided by the reference diameter and multiplied by 100); and 5) late luminal loss (difference between minimum lumen diameter at the end of the procedure and minimum lumen diameter at follow-up). Quantitative analysis was performed in the in-stent area (inside the stented segment) and in the in-lesion segment, including the stented area as well as 5 mm both proximally and distally to the stent. In-stent and in-lesion restenoses were defined as 50% diameter stenosis at follow-up located within the stent and the target lesion, respectively.

IVUS analysis.   The IVUS studies were performed immediately after the procedure and at follow-up, after intracoronary administration of 100 to 200 µg nitroglycerin.

All IVUS studies were performed with a motorized automatic transducer pullback system (0.5 mm/s) and commercially available scanners (i-Lab, Boston Scientific Corporation, Natick, Massachusetts) consisting of a rotating 40-MHz transducer catheter (Atlantis SR pro) with a 2.6-F imaging sheath. The images were digitalized for off-line quantitative analysis according to the American College of Cardiology's Clinical Expert Consensus Document on IVUS. Quantitative IVUS analysis was made using a commercially available computerized planimetry program (EchoPlaque, INDEC Systems, Mountain View, California).

Quantitative parameters of lumen, stent, and vessel (external elastic membrane) cross-sectional areas were determined. The neointimal area was calculated as the stent area minus the lumen area at follow-up. Late lumen area loss was calculated as the minimum lumen area after initial stent deployment minus the minimum lumen area within the stented segment at follow-up. Lumen, stent, vessel, and neointimal volumes were calculated using Simpson's rule. Percent of neointimal volume obstruction was determined by the neointimal volume at follow-up divided by the follow-up stent volume and multiplied by 100.

Incomplete stent apposition was defined as 1 stent strut clearly separated from the vessel wall with evidence of blood speckles behind the struts, and was classified as follows: 1) persistent (when present both in the post-stent implantation and follow-up studies); 2) late acquired (when not present at post-stent implantation, but detectable at the follow-up study); and 3) resolved (when present at post-stent implantation, but not detectable at the follow-up study).

Both QCA and IVUS analyses were performed by independent core laboratories at Cardiovascular Research Center (São Paulo, Brazil).

Study end points.   The primary end points of this analysis were in-stent luminal late loss as measured by QCA and in-stent percentage volume obstruction by IVUS, measured at 4-month angiographic follow-up. Secondary end points included acute success (angiographic and procedure success), cumulative rate of major adverse cardiac events up to 2 years, rates of target lesion and target vessel revascularization up to 2 years, and in-stent volumetric neointimal burden by IVUS at 4 and 8 months.

Device success was defined by the presence of residual stenosis <20% in the treated segment, in the presence of Thrombolysis In Myocardial Infarction (TIMI) flow grade 3 after implantation of the VES. Procedure success was defined by device success associated with no in-hospital major adverse events. A major adverse cardiac event was defined as death, nonfatal myocardial infarction (Q-wave and non–Q-wave), and need for repeat lesion revascularization (by new percutaneous intervention or coronary artery bypass graft surgery). All deaths were considered cardiac unless a clear noncardiac reason was identified. Myocardial infarction was defined by an increase in the CK-MB twice the upper the normal limit with or without new Q waves on the electrocardiogram.

Statistical analysis.   Continuous variables are expressed as mean ± SD. Comparisons between post-intervention and follow-up measurements were performed with a 2-tailed paired t test. A p value < 0.05 was considered statistically significant.

	Results

Top Abstract Methods Results Discussion Conclusions REFERENCES

 
During May 2007, a total of 15 consecutive patients who matched the inclusion/exclusion criteria were treated with the Vestasync eluting stent and included in this analysis. The mean age was 63.8 years (± 1.4 years), and 40% were women. Diabetes mellitus was present in 33% of the cases. The left anterior descending artery was the target vessel in most cases (47%) (Table 1).

Post-procedure and 4-month QCA and IVUS results are displayed in Tables 2 and 3. One IVUS study was deemed inappropriate for analysis (poor image quality), and therefore the patient was excluded from the IVUS baseline/follow-up comparison. Binary restenosis (in-stent stenosis 50%) was not observed in any these patients by QCA, and no patient had more than 10% neointimal proliferation at IVUS. Two cases of acute incomplete stent apposition were observed in the baseline procedure and were significantly reduced at 4-month follow-up. Figure 2 exemplifies the best and worst results of the patients enrolled in this study.

View larger version (36K): [in this window] [in a new window] [Download PPT slide]   Figure 2 Examples From Our Initial Experience Two examples of our first-in-human series of patients treated with the Vestasync stent. Panel A demonstrates the case with higher late lumen loss at 4 months (0.80 mm). Panel B demonstrates our best results (late lumen loss of –0.1 mm). FU = follow-up; POST = post-procedure; PRE = pre-procedure.

	Discussion

Top Abstract Methods Results Discussion Conclusions REFERENCES

 
The main finding of this first-in-human study with the non–polymer-based VES is that sirolimus can be efficiently delivered to the coronary artery without a durable polymer, as demonstrated by the minimum neointimal growth noted at QCA and IVUS.

The development of novel DES systems must be guided by 2 main rationales: 1) to achieve an improved safety profile, and 2) to improve or at least keep the efficacy profile at levels comparable to those of the existing DES devices.

The DES toxicity may be related mainly to 2 aspects: dose/type of the antiproliferative agent delivered to the coronary artery and presence/type of polymer used to carry the antiproliferative drug. In this context, the novel VES carries less than one-half of the dose of the first-generation Cypher sirolimus-eluting stent. As previously demonstrated by Nakamura et al. (22), it is possible to keep the same efficacy of the Cypher stent using 70% or even 45% of its original dose. In a study conducted by that group with 44 patients treated with the Cypher stent at reduced doses, angiographic and ultrasonographic results were comparable to those obtained after the full-dose Cypher implantation (22). Our current analysis supports their findings.

A few recent clinical reports have correlated the presence of durable polymers to local vessel response (e.g., marked positive remodeling in the treated segment), and of more importance, some potentially life-threatening cases of late and very late stent thrombosis have been described. These clinical findings have also been associated with local inflammatory response, as noted in post-mortem studies (23,24).

At present, 4 different DES are FDA approved (Cypher, Taxus, Endeavor, and Promus/Xience V). Apart from the Endeavor, which uses a biocompatible polymer (phosphorycholine) to carry the zotarolimus, the other 3 systems use durable polymers. The Endeavor, though, is the DES that elicits more neointimal proliferation, as consistently demonstrated in all clinical studies (roughly 0.6 mm) (25). The other 3 DES presented late loss ranging from 0.1 to 0.4 mm in their clinical series (Fig. 3) (26–28). As demonstrated by Mauri et al. (29), there are incremental steps in binary restenosis as in-stent late loss increases. According to the mathematical model proposed by their group, a rise from 0.2 to 0.4 mm would result in an increase in restenosis rate by 3.1%, whereas an increase in late loss from 0.4 to 0.6 mm would result in an augmentation in the expected restenosis rate by 6.4%.

View larger version (19K): [in this window] [in a new window] [Download PPT slide]   Figure 3 Late Lumen Loss of Vestasync Stent Versus the FDA-Approved DES Late loss results reported for the Food and Drug Administration (FDA)–approved drug-eluting stent (DES) in contrast to the findings of the current analysis. When compared to the published results of other DES tested in similar scenarios, the in-stent late loss of the Vestasync stent is equivalent to that of the Endeavor and Taxus stents and slightly higher than that of the Cypher and Xience/Promus stents. *Invasive follow-up done at 4 months. **Invasive follow-up done at 6 months. FIM = first-in-man; SPIRIT = Stroke Prevention in Reversible Ischemia Trial.

Currently ongoing, the multicenter Vestasync 2 trial will compare, in a randomized fashion, patients treated with the VES (n = 90) to its noneluted equivalent, the GenX stent (n = 30).

Study limitations.   This study comprises a registry of only 15 patients with noncomplex coronary lesions with 6-month clinical follow-up. Considering the virtual absence of late loss (by QCA) and neointimal formation (by IVUS) at 4-month invasive follow-up, however, these results seem to be very promising. Nine-month angiography and IVUS will be performed in all patients to assess whether these preliminary findings are sustained; moreover, patients will be clinically followed up for 3 years. The 4-month follow-up of 15 patients precludes any definite conclusion about the long-term safety of this device.

	Conclusions

Top Abstract Methods Results Discussion Conclusions REFERENCES

 
The third-generation Vestasync hydroxyapatite non-polymer-based sirolimus-eluting stent system was proved feasible and safe, and elicited minimum neointimal proliferation at 4-month follow-up. These favorable preliminary results require further confirmation by large, randomized, multicenter clinical studies with longer follow-up.

	Footnotes

 
Dr. Bonan and Dr. Alexandre Abizaid serve as consultants for MIV Therapeutics, Inc. James Hermiller, MD, served as Guest Editor for this paper.

^_* Reprint requests and correspondence: Dr. Alexandre Abizaid, Instituto Dante Pazzanese De Cardiologia, Av. Dr. Dante Pazzanese, 500 Ibirapuera, São Paulo-SP, Brazil 04012-909 (Email: aabizaid{at}uol.com.br).

Manuscript received April 25, 2008; revised manuscript received July 14, 2008, accepted July 28, 2008.

	REFERENCES

Top Abstract Methods Results Discussion Conclusions REFERENCES

 

1. 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]
2. Stettler C, Wandel S, Allemann S, et al. Outcomes associated with drug-eluting and bare-metal stents: a collaborative network meta-analysis Lancet 2007;370:937-948.[CrossRef][Web of Science][Medline]
3. Feres F, Costa Jr. JR, Abizaid A. Very late thrombosis after drug-eluting stents Catheter Cardiovasc Interv 2006;68:83-88.[CrossRef][Web of Science][Medline]
4. Beohar N, Davidson CJ, Kip KE, et al. Outcomes and complications associated with off-label and untested use of drug-eluting stents JAMA 2007;297:1992-2000.[Abstract/Free Full Text]
5. Lagerqvist B, James SK, Stenestrand U, Lindbäck J, Nilsson T, Wallentin L, 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]
6. Lüscher 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]
7. Nebeker JR, Virmani R, Bennett CL, et al. Hypersensitivity cases associated with drug-eluting coronary stents: a review of available cases from the Research on Adverse Drug Events and Reports (RADAR) project J Am Coll Cardiol 2006;47:175-181.[Abstract/Free Full Text]
8. Cook S, Wenaweser P, Togni M, et al. Incomplete stent apposition and very late stent thrombosis after drug-eluting stent implantation Circulation 2007;115:2426-2434.[Abstract/Free Full Text]
9. Siqueira DA, Abizaid AA, Costa J de R, et al. Late incomplete apposition after drug-eluting stent implantation: incidence and potential for adverse clinical outcomes Eur Heart J 2007;28:1304-1309.[Abstract/Free Full Text]
10. Eppley BL, Pietrzak W, Blanto MW. Allograft and alloplastic bone substitutes: a review of science and technology for the craniomaxillofacial surgeon J Craniofacial Surg 2005;16:981-989.[CrossRef][Web of Science][Medline]
11. Jarcho M. Retrospective analysis of hydroxyapatite development for oral implant applications Dental Clin North Am 1992;36:19-26.
12. Butler Manuel PA, James SE, Shepperd JA. Pelvic underpinning: 8 years experience Br J Bone Joint Surg 1992;74B:74-77.[Web of Science][Medline]
13. Shepperd JAN, Apthorp H. A contemporary snapshot of the use of hydroxyapatite coating in orthopaedic surgery Br J Bone Joint Surg 2005;87B:1046-1049.[CrossRef][Medline]
14. Pezzatini S, Solito R, Morbidelli L, et al. The effect of hydroxyapatite nanocrystals on microvascular endothelial cell viability and functions J Biomed Mater Res 2006;76:656-663.
15. Groth CG, Backman L, Morales JM, et al. Sirolimus (rapamycin)-based therapy in human renal transplantation: similar efficacy and different toxicity compared with cyclosporine. Sirolimus European Renal Transplant Study Group. Transplantation 1999;67:1036-1042.[Web of Science][Medline]
16. Marx SO, Jayaraman T, Go LO, et al. Rapamycin-FKBP inhibits cell cycle regulators of proliferation in vascular smooth muscle cells Circ Res 1995;76:412-417.[Abstract/Free Full Text]
17. Poon M, Marx SO, Gallo R, et al. Rapamycin inhibits vascular smooth muscle cell migration J Clin Invest 1996;98:2277-2283.[Web of Science][Medline]
18. Gregory CR, Huang X, Pratt RE, et al. Treatment with rapamycin and mycophenolic acid reduces arterial intimal thickening produced by mechanical injury and allows endothelial replacement Transplantation 1995;59:655-661.[Web of Science][Medline]
19. Burke SE, Lubbers NL, Chen YW, et al. Neointimal formation after balloon-induced vascular injury in Yucatan minipigs is reduced by oral rapamycin J Cardiovasc Pharmacol 1999;33:829-835.[CrossRef][Web of Science][Medline]
20. Gallo R, Padurean A, Jayaraman T, et al. Inhibition of intimal thickening after balloon angioplasty in porcine coronary arteries by targeting regulators of the cell cycle Circulation 1999;99:2164-2170.[Abstract/Free Full Text]
21. Ryan TJ, Faxon DP, Gunnar RM, et al. Guidelines for percutaneous transluminal coronary angioplasty. A report of the American College of Cardiology/American Heart Association Task Force on assessment of diagnostic and therapeutic cardiovascular procedures (subcommittee on percutaneous transluminal coronary angioplasty). Circulation 1988;78:486-502.[Free Full Text]
22. Nakamura M, Abizaid A, Hirohata A, Honda Y, Sousa JE, Fitzgerald PJ. Efficacy of reduced-dose sirolimus-eluting stents in the human coronary artery: serial IVUS analysis of neointimal hyperplasia and luminal dimension Catheter Cardiovasc Interv 2007;70:946-951.[CrossRef][Web of Science][Medline]
23. Virmani R, Farb A, Guagliumi G, Kolodgie FD. Drug-eluting stents: caution and concerns for long-term outcome Cor Artery Dis 2004;15:313-318.[CrossRef][Web of Science][Medline]
24. 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]
25. Meredith IT, Ormiston J, Whitbourn R, et al. First-in-human study of the Endeavor ABT-578-eluting phosphorylcholine-encapsulated stent system in de novo native coronary artery lesions: Endeavor I Trial EuroInterv 2005;1:157-164.
26. Sousa JE, Costa MA, Abizaid A, et al. Lack of neointimal proliferation after implantation of sirolimus-coated stents in human coronary arteries: a quantitative coronary angiography and three-dimensional intravascular ultrasound study Circulation 2001;103:192-195.[Abstract/Free Full Text]
27. Serruys PW, Ong ATL, Piek JJ, et al. A randomized comparison of a durable polymer everolimus-eluting stent with a bare metal coronary stent: the SPIRIT first trial EuroInterv 2005;1:58-65.
28. Grube E, Silber S, Hauptmann KE, et al. Taxus I: six- and twelve-month results from a randomized, double-blind trial on a slow-release paclitaxel-eluting stent for de novo coronary lesions Circulation 2003;107:38-42.[Abstract/Free Full Text]
29. Mauri L, Orav EJ, Kuntz RE. Late loss in lumen diameter and binary restenosis for drug-eluting stent comparison Circulation 2005;111:3435-3442.[Abstract/Free Full Text]

This article has been cited by other articles:

				S. R. Dixon, C. L. Grines, and W. W. O'Neill The year in interventional cardiology. J. Am. Coll. Cardiol., June 2, 2009; 53(22): 2080 - 2097. [Full Text] [PDF]

				J. R. Costa Jr, A. Abizaid, R. Costa, F. Feres, L. F. Tanajura, A. Abizaid, G. Maldonado, R. Staico, D. Siqueira, A. G.M.R. Sousa, et al. 1-Year Results of the Hydroxyapatite Polymer-Free Sirolimus-Eluting Stent for the Treatment of Single De Novo Coronary Lesions: The VESTASYNC I Trial J. Am. Coll. Cardiol. Intv., May 1, 2009; 2(5): 422 - 427. [Abstract] [Full Text] [PDF]

This Article Abstract Figures Only Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Services Email this article to a friend Similar articles in this journal Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Costa, J. R. Articles by Sousa, J. E. Search for Related Content PubMed Articles by Costa, J. R., Jr Articles by Sousa, J. E.