The Current Status of Stent Placement in Small Coronary Arteries
< 3.0 mm in Diameter

Stent placement in coronary arteries >= 3.0 mm in diameter has been irrefutably proven to be superior to conventional balloon angioplasty (PTCA) in reducing the risk of restenosis and major adverse cardiac events.1–4 Subsequent improvements in stenting technique and antithrombotic regimen have dramatically reduced the incidence of stent thrombosis.5–9 These favorable outcomes in concert have resulted in an exponential rise in the volume of stent-related procedures and have extensively broadened the indications for stenting to encompass non-STRESS/BENESTENT lesions, including, among others, lesions in small coronary arteries (Early angiographic and clinical outcome after SVS. Stent thrombosis (ST) remains a dreaded complication of stenting, since its clinical consequences, including a risk of death in up to 25% and myocardial infarction in 60–70% of cases, are generally catastrophic.14–17 The risk of ST appears to be accentuated in the presence of certain potentially adverse clinical, anatomic, rheologic and stent-related factors.14–17 In particular, SVS has been previously cited as a risk factor for ST.14–21 In a study by Agrawal et al.,20 ST was documented to be significantly higher in patients who received Gianturco-Roubin stents = 3.0 mm in diameter (13% versus 2%; p = 0.0002); an even higher ST rate was observed after stenting with 2.0 mm Gianturco-Roubin stents.19 A similar finding was observed after SVS with the Palmaz-Schatz stent.21 Such a relationship no longer holds true; current strategies of optimal stent deployment and aggressive antiplatelet, warfarin-free antithrombotic regimens appear to have resolved this problem.5–9 SVS is now associated with the same risk of ST as larger vessel stenting (about 1–2%).12,16,22 The Milan investigators5,6 clearly demonstrated that ST is closely linked with stent underexpansion and that this risk could be significantly decreased with optimal stent expansion. In a recent study by Cheneau et al.23 on a large group of patients, intravascular ultrasound (IVUS)-determined vessel size and reference segment disease were not important predictors of ST; only final lesion site parameters — dissection, thrombus, tissue prolapse and lumen dimensions — were critical contributors of ST. Advances in stent technology have also produced devices with lower profiles (Figure 1), greater flexibility and trackability, and thinner struts designed to achieve optimal radial force at a smaller diameter. These customized stents were recently used in several trials comparing SVS with PTCA.24–32 Procedural success rate was equivalent or better in the stent-treatment arm compared to the PTCA-treatment arm in these trials; a significant proportion of patients (14–37%) assigned to PTCA had to undergo stent placement for the treatment of suboptimal angiographic results or acute/threatened closures. The acute luminal gain was also significantly greater in the stent group compared to the PTCA group. Long-term angiographic and clinical outcomes after SVS. Previous data clearly showed an inverse relationship between vessel size and the risk of restenosis (and cardiac events) following intervention with non-stent devices.13,33–37 In the M-Heart study,33 restenosis rate after PTCA for vessels with reference diameter 2.9 mm (p = 0.036). In the STRESS I-II trial,35 restenosis rate following PTCA for vessels = 3.0 mm after directional coronary atherectomy.37 It was hoped that stent placement might circumvent the disadvantages that exist with non-stent devices by providing a more pristine immediate luminal outcome, more favorable rheology, the biggest luminal gain of all interventional devices and by virtually eliminating any recoil and vascular remodeling seen in non-stent devices. Unfortunately, these theoretical benefits of stents were not borne out by initial results.12,22,38–40 Elezi et al.38 showed a steady increase in binary restenosis rate (and major cardiac events) with decreasing vessel size. The restenosis rates were 38.6% for vessels 3.2 mm in diameter (p = 3.0 mm was 19.9%, compared to 32.6% for smaller vessels (p 2.6 mm (p = 0.018). This is not entirely surprising, considering that it takes a smaller volume of intimal hyperplasia to induce a diameter stenosis of greater than 50% in a smaller vessel than a larger one. There is also a tendency to apply higher balloon pressures and oversized stents in SVS, leading to more vessel stretch and more vessel injury, both of which have been shown to be associated with more intimal hyperplasia.41,42 Intimal hyperplasia is the mainstay mechanism of in-stent restenosis.43 Furthermore, there is evidence to indicate that pre- and post-interventional plaque burden are strong predictors of in-stent restenosis and plaque burden is greater in small vessels than larger vessels.44 These observational data created a clinical conundrum and cast doubt regarding the superiority of systematic stent placement over PTCA in small vessels. However, results of post hoc quantitative angiographic analysis of the STRESS I-II trial35 did not support this observation and were in favor of SVS; it showed that stent placement was associated with a 38% relative reduction in restenosis and a 33% reduction in clinical events compared with PTCA. This encouraging finding was questioned, since the trial and the stents used in the trial were primarily designed for large vessels. Several randomized trials were thus commenced to compare “customized” stents and PTCA in small coronary arteries (Figure 2).24–32 These stents were specifically made to fit vessels 2.8 mm in diameter in 651 patients. The Multi-Link stent (strut thickness, 0.05 mm) was associated with a 42% reduction in 6-month restenosis rate (15.0% versus 25.8%, respectively; p = 0.003) as a result of a lower late loss (0.94 mm versus 1.17 mm, respectively; p = 0.001) and a 38% reduction in 1-year target vessel revascularization rate (8.6% versus 13.8%, respectively; p = 0.03) compared with the thicker strut Duet stent (0.14 mm). In an observational study by Briguori et al.,47 stents with strut thickness = 0.1 mm in vessels Coated stents. Different surface properties may significantly influence the stent interaction with the arterial wall and circulating blood.45 Coating stents with other materials (metals, polymers, biological materials or drugs) has the potential to improve the functionality, biocompatibility and overall performance of the stent. In addition, coating stents with certain materials may improve the surface texture and smoothness, which may in turn influence the risk of thrombosis and the degree of intimal hyperplasia.49,50 Unfortunately, in practice, most stent coatings tested have failed to confer any advantage over uncoated stainless-steel stents. In several randomized trials,51–54 gold-coated stents were found to be inferior to uncoated stents; the former stent model was associated with an increased risk of stent thrombosis and in-stent restenosis. Phosphorylcholine, a nonallergenic, naturally occurring substance with the potential to decrease platelet and thrombus formation and to elicit less adverse tissue response compared with synthetic polymers,45 has been investigated in 2 large-sized randomized trials.55,56 Its theoretical benefits were not evident in these trials; there was no difference in the restenosis rate between the phosphorylcholine-coated stent cohort and the bare metal stent (BMS) cohort, and a suggestion of an increased risk of stent thrombosis. Heparin coating of stents has also been studied in humans; again, there was no clear-cut evidence that it reduced stent thrombosis or restenosis.31,57 Stent coating is also an elegant method of performing site-specific local drug delivery to the target lesion to modify the vascular response following angioplasty injury and to reduce intimal hyperplasia. The application of drug-eluting stents is a novel approach of achieving this aim by synergistically combining the mechanical scaffolding action of metallic stents and the anti-thrombotic and antiproliferative effect of various drugs locally delivered at adequate concentrations without the danger of systemic toxicity. As alluded to earlier, in-stent restenosis continues to plague about 30% of stents placed in small vessels as a result of exuberant smooth muscle cell proliferation and accumulation of intercellular matrix. The strategy of coating stent surfaces with immunosuppressive agents to combat the adverse sequelae of angioplasty-related injury has been shown to be effective in animal studies.58–61 Of these drugs, sirolimus and paclitaxel appear most promising to date. Sirolimus, a lipophilic, macrolide antifungal agent, induces cell-cycle arrest, prevents cell replication without producing cell death, inhibits smooth muscle cell proliferation and migration, and has anti-inflammatory properties.62 These experimental benefits of sirolimus were recently clinically proven in the RAVEL trial,63 which randomized 238 patients with lesions in native coronary arteries between 2.5–3.5 mm in diameter to treatment with either sirolimus-eluting stents (SES) or BMS (Table 1). In this trial, sirolimus was able to virtually eliminate in-stent neointimal hyperplasia, thereby dramatically reducing the restenosis rate (0% versus 26.6% in the BMS cohort; p = 15 mm), the risk reduction for in-segment restenosis was 64.5%, compared to a risk reduction of 81.7% in non-diabetics with short lesions (= 3.0 mm). The most recently completed European66 and Canadian67 SIRIUS trials reaffirmed and extended the findings in the RAVEL and SIRIUS trials by clearly demonstrating the efficacy of this novel device in smaller vessels (Table 1) without an increased risk of stent thrombosis (about 1%). The E-SIRIUS trial66 is a multicenter European trial that randomly assigned 177 patients to receive the Bx Velocity stent (Cordis Corporation) and 175 patients to receive the sirolimus-coated Cypher stent (Cordis Corporation). The stents were implanted in native coronary arteries of reference diameter between 2.5 mm and 3.0 mm by visual estimate. The 8-month follow-up angiogram showed a 86% reduction in the in-segment restenosis rate with the use of SES (5.9% versus 42.3% in the BMS group; p Conclusion. A number of conclusions can be drawn from the data accrued to date with regard to SVS. First, stent placement (provisional stenting) is definitely safe and useful when used in the setting of suboptimal results after PTCA in small vessels; in fact, it may also be life-saving in the face of threatened or acute closure. ST can be largely avoided with the use of optimal stenting techniques and aggressive dual antiplatelet post-stent regimens. Second, systematic SVS with the use of BMS is at worst equivalent to PTCA, and at best, superior to PTCA in its mid-term angiographic and clinical outcomes. The potential for PTCA in small vessels appears to be exhausted; even with the most optimal luminal outcome, this treatment modality can only offer a mid-term outcome that is equivalent to stenting. Having said that, however, stent placement may be avoided in the presence of “stent-like” luminal results after PTCA. Third, stent structure and configuration appear to play a crucial role in determining its acute and long-term outcomes. Tubular or corrugated stainless-steel stents are better than coil or meshwire stent models. Stents with thinner struts and lower metal density yield a lower risk of restenosis than those with thicker struts and are preferred for SVS. The availability of newer, highly biocompatible and more radiovisible alloys with the same if not superior tensile strength compared to stainless-steel will enable the production of low metal density stents that may further improve on the anatomic and clinical outcomes of current stainless-steel stents. Fourth, gold-plated stents are best avoided because of their enhanced risk of restenosis. Coating stents with phosphorylcholine and heparin does not appear to confer any advantage over bare stents. In contradistinction, stents coated with highly efficacious antiproliferative agents (in particular, sirolimus and paclitaxel) hold considerable promise. As a whole, these DESs have yielded restenosis rates that are unrivaled by other stent models. However, several important questions regarding DES need to be addressed before prematurely “burying BMS alive.” Can the clinical benefits of DES fully justify its high cost, or should its use be restricted to only selected high-risk clinico-anatomic settings? Are they safe and are their early profound salutary effects durable over several years or are they simply delaying restenosis? The role of the basic design and structure of stents on which these drugs are coated and the comparative efficacy of various antirestenotic drugs used for stent coating also remain unclear at this stage. The ideal DES design may need to have a large surface area of contact with the vascular wall, minimal interfilament gaps, robust radial support and symmetrical expansion to ensure uniform drug elution. At the same time, it would need to be slim, flexible and conformable to maintain deliverability in complex lesions. For drugs with narrow toxic-therapeutic index, customized stent platform may be required. Hence, before we proceed to drastically and profoundly alter our interventional cardiology practice patterns, we should wait for answers to some of these questions about DES. Having said that, it is entirely foreseeable that most interventional procedures in the near future will involve DESs in one form or another, perhaps containing sirolimus, paclitaxel or an even more effective drug with both antimitotic and antithrombotic actions, impregnated onto a highly biocompatible carrier vehicle without adverse tissue effects, and mounted onto a stent design with uniform expansion and with programmable, controllable drug-eluting capability.

1. Fischman DL, Leon MB, Baim DS, et al., for the Stent Restenosis Study Investigators. A randomized comparison of coronary stent placement and balloon angioplasty in the treatment of coronary artery disease. N Engl J Med 1994;331:496–501. 2. Serruys PW, de Jaegere P, Kiemeneij F, et al., for the Benestent Study Group. A comparison of balloon expandable stent implantation with balloon angioplasty in patients with coronary artery disease. N Engl J Med 1994;331:489–495. 3. Macaya C, Serruys PW, Ruygrok P, et al. Continued benefit of coronary stenting versus balloon angioplasty: One-year clinical follow-up of BENESTENT trial. J Am Coll Cardiol 1996;27:255–261. 4. Betriu A, Masotti M, Serra A, et al. Randomized comparison of coronary stent implantation and balloon angioplasty in the treatment of de novo coronary artery lesions (START): A four-year follow-up. J Am Coll Cardiol 1999;34:1498–1506. 5. Nakamura S, Colombo A, Gaglione A, et al. Intracoronary ultrasound observations during stent implantation. Circulation 1994;89:2026–2034. 6. Colombo A, Hall P, Nakamura S, et al. Intracoronary stenting without anticoagulation accomplished with intravascular ultrasound guidance. Circulation 1995;91:1676–1688. 7. Moussa I, Di Mario C, Di Francesco L, et al. Subacute stent thrombosis and the anticoagulation controversy: Changes in drug therapy, operator technique and the impact of intravascular ultrasound. Am J Cardiol 1996;78(Suppl 3A):13–17. 8. Schömig A, Neumann FJ, Kastrati ZA, et al. A randomized comparison of antiplatelet and anticoagulant therapy after the placement of coronary-artery stents. N Engl J Med 1996;334:1084–1089. 9. Leon MB, Baim DS, Popma JJ, et al. A clinical trial comparing three antithrombotic-drug regimens after coronary-artery stenting: Stent Anticoagulation Restenosis Study Investigators. N Engl J Med 1998;339:1665–1671. 10. Lip GYH, Rathore VS, Katira R, et al. Do Indo-Asians have smaller coronary arteries? Postgrad Med J 1999;886:463–466. 11. Heldman AW, Brinker JA. Stenting small coronaries: Size does matter. Cathet Cardiovasc Intervent 1999;47:277–278. 12. Lau KW, Ding ZP, Sim LL, Sigwart U. Clinical and angiographic outcome after angiography-guided stent placement in small coronary vessels. Am Heart J 2000;139:830–839. 13. Kuntz RE, Gibson CM, Nobuyoshi M, Baim DS. Generalized model of restenosis after conventional balloon angioplasty, stenting and directional atherectomy. J Am Coll Cardiol 1993;21:15–25. 14. Karrillon GJ, Morice MC, Benveniste E, et al. Intracoronary stent implantation without ultrasound guidance and with replacement of conventional anticoagulation by antiplatelet therapy: 30-day clinical outcome of the French Multicenter Registry. Circulation 1996;94:1519–1527. 15. Mak KH, Belli G, Ellis SG, Moliterno DJ. Subacute stent thrombosis: Evolving issues and current concepts. J Am Coll Cardiol 1996;27:494–503. 16. Moussa I, Di Mario C, Reimers B, et al. Subacute stent thrombosis in the era of intravascular ultrasound-guided coronary stenting without anticoagulation: Frequency, predictors and clinical outcome. J Am Coll Cardiol 1997;29:6–12. 17. Cutlip DE, Baim DS, Ho KK, et al. Stent thrombosis in the modern era: A pooled analysis of multicenter coronary-stent clinical trials. Circulation 2001;103:1967–1971. 18. Roubin GS, Cannon AD, Agrawal SK, et al. Intracoronary stenting for acute and threatened closure complicating percutaneous transluminal coronary angioplasty. Circulation 1992;84:916–927. 19. George BS, Voorhees WD, Roubin GS, et al. Multicenter investigation of coronary stenting to treat acute or threatened closure after percutaneous transluminal coronary angioplasty: Clinical and angiographic outcomes. J Am Coll Cardiol 1993;22:135–143. 20. Agrawal SK, Ho SW, Liu MW, et al. Predictors of thrombotic complications after placement of the flexible coil stent. Am J Cardiol 1994;73:1216–1219. 21. Rosenman Y, Lotan C, Mosseri M, Gotsman MS. Relation of thrombotic occlusion of coronary stents to the indication for stenting, stent size and anticoagulation. Am J Cardiol 1995;75:84–85. 22. Akiyama T, Moussa I, Reimers B, et al. Angiographic and clinical outcome following coronary stenting of small vessels: A comparison with coronary stenting of large vessels. J Am Coll Cardiol 1998;32:1610–1618. 23. Cheneau E, Leborgne L, Mintz GS, et al. Predictors of subacute stent thrombosis. Results of a systematic intravascular ultrasound study. Circulation 2003;108:43–47. 24. Savage MP, Fischman DL, Kada F, et al. A randomized comparison of elective stenting and balloon angioplasty in the treatment of small coronary arteries (Abstr). Circulation 1999;100(Suppl-I):1503. 25. Park SW, Lee CW, Hong MK, et al. Randomized comparison of coronary stenting with optimal balloon angioplasty for treatment of lesions in small coronary arteries. Eur Heart J 2000;21:1785–1789. 26. Kastrati A, Schömig A, Dirschinger J, et al., for the ISAR-SMART Study Investigators. A randomized trial comparing stenting with balloon angioplasty in small vessels in patients with symptomatic coronary artery disease. Circulation 2000;102:2593–2598. 27. Moer R, Myreng Y, Molstad P, et al. Stenting in small coronary arteries (SISCA) trial. J Am Coll Cardiol 2001;38:1598–1603. 28. Doucet S, Schalij MJ, Vrolix MCM, et al., for the Stent in Small Arteries (SISA) Trial Investigators. Stent placement to prevent restenosis after angioplasty in small coronary arteries. Circulation 2001;104:2029–2033. 29. Koning R, Eltchaninoff H, Commeau P, et al., for the BESMART (BeStent in Small Arteries) Trial Investigators. Circulation 2001;104:1604–1608. 30. Garcia E, Gomez-Recio M, Moreno R, et al. Stent reduces restenosis in small vessels: Results of the RAP study (Abstr). J Am Coll Cardiol 2001;37:17A. 31. Haude M, Konorza TFM, Kalnins U, et al. Heparin-coated stent placement for the treatment of stenoses in small coronary arteries of symptomatic patients. Circulation 2003;107:1265–1270. 32. Muramatsu T. Coronary heart disease stenting in small vessel versus balloon angioplasty study (CHIVAS). A randomized prospective multicenter trial. Presented at Transcatheter Cardiovascular Therapeutics, Washington, D.C., 2002. 33. Hirshfeld JW, Schwartz SS, Jugo R, et al. Restenosis after coronary angioplasty: A multivariate statistical model to relate lesion and procedural variables to restenosis. J Am Coll Cardiol 1991;18:647–756. 34. Foley DP, Melkert R, Serruys PW. Influence of coronary vessel size on renarrowing process and late angiographic outcome after successful balloon angioplasty. Circulation 1994;90:1239–1251. 35. Savage MP, Fischman DL, Rake R, et al., for the Stent Restenosis Study (STRESS) Investigators. Efficacy of coronary stenting versus balloon angioplasty in small coronary arteries. J Am Coll Cardiol 1998;31:307–311. 36. Kuntz RE, Safian RD, Carrozza JP, et al. The importance of acute luminal diameter in determining restenosis after coronary atherectomy or stenting. Circulation 1992;86:1827–1835. 37. Hinohara T, Robertson GC, Selmon MR, et al. Restenosis after directional coronary atherectomy. J Am Coll Cardiol 1992;20:623–632. 38. Elezi S, Kastrati A, Neumann FJ, et al. Vessel size and long-term outcome after coronary stent placement. Circulation 1998;98:1875–1880. 39. Bauters C, Hubert E, Prat A, et al. Predictors of restenosis after coronary stent implantation. J Am Coll Cardiol 1996;31:1291–1298. 40. Kasaoka S, Tobis JM, Akiyama T, et al. Angiographic and intravascular ultrasound predictors of instent restenosis. J Am Coll Cardiol 1998;32:1630–1635. 41. Schwartz RS, Murphy JG, Edwards WD, et al. Restenosis after balloon angioplasty: A practical proliferative model in porcine coronary arteries. Circulation 1990;82:2190–2200. 42. Hoffmann R, Mintz GS, Mehran R, et al. Tissue proliferation within and surrounding Palmaz-Schatz stents is dependent on the aggressiveness of stent implantation technique. Am J Cardiol 1999;83:1170–1174. 43. Hoffmann R, Mintz GS, Dussaillant GR, et al. Patterns and mechanisms of in-stent restenosis: A serial intravascular ultrasound study. Circulation 1996;94:1247–1254. 44. Hoffmann R, Mintz GS, Mehran R, et al. Intravascular ultrasound predictors of angiographic restenosis in lesions treated with Palmaz-Schatz stents. J Am Coll Cardiol 1998;31:43–49. 45. Lau KW, Mak KH, Hung JS, Sigwart U. The clinical impact of stent construction and design in percutaneous coronary intervention. Am Heart J 2004;147:764–773. 46. Kastrati A, Mehilli J, Dirschinger J, et al. Intracoronary stenting and angiographic results. Strut thickness effect on restenosis outcome (ISAR-STEREO) trial. Circulation 2001;103:2816–2821. 47. Briguori C, Sarais C, Pagnotta P, et al. In-stent restenosis in small coronary arteries. Impact of strut thickness. J Am Coll Cardiol 2002;40:403–409. 48. Kastrati A, Schuhlen H, Schömig A. Stenting for small coronary vessels: A contestable winner (editorial). J Am Coll Cardiol 2001;38:1604–1607. 49. Hehrlein C, Zimmermann M, Metz J, et al. Influence of surface texture and charge on the biocompatibility of endovascular stents. Coron Artery Dis 1995;6:581–586. 50. Edelman ER, Seifert P, Groothuis A, et al. Gold-coated NIR stents in porcine coronary arteries. Circulation 2001;103:429–434 51. Kastrati A, Schömig A, Dirschinger J, et al. Increased risk of restenosis after placement of gold-plated stents. Circulation 2000;101:2478–2483. 52. Reifert N, Morice MC, Silbers S, et al. The NUGGET trial: NIR Ultimate Gold-Gilded Equivalency Trial. Cathet Cardiovasc Intervent 2004;62:18–25. 53. Park SJ, Lee CW, Hong MK, et al. Comparison of gold-coated NIR stents with uncoated NIR stents in patients with coronary artery disease. Am J Cardiol 2002;89:872–875. 54. Silber S. Final results of the NIRTOP trial. Presented at the EuroPCR Symposium, Paris, France, 2003. 55. Moses JW, Buller CEH, Nukta ED, et al. The first clinical trial comparing a coated versus a noncoated coronary stent: The Biocompatibles BiodivYsio stent in randomized control trial (DISTINCT) (Abstr). Circulation 2000;101(Suppl II):664. 56. Hausleiter J, Kastrati A, Mehilli J, et al. A randomized trial comparing phosphorylcholine-coated stents with balloon angioplasty in small coronary arteries in patients with symptomatic coronary artery disease. The ISAR-SMART 2 trial (Abstr). Circulation 2003;108(Suppl IV):569. 57. Wohrle J, Al-Khayer U, Grotzinger C, et al. Comparison of the heparin-coated versus the uncoated Jostent — No influence of restenosis or clinical outcome. Eur Heart J 2001;22:1808–1816. 58. Marx SO, Jayaram T, Go LO, Marks AR. Rapamycin-FKBP inhibits cell cycle regulators of proliferation in vascular smooth muscle cells. Circ Res 1995;76:412–417. 59. Morris R, Cao W, Huang X, et al. Rapamycin (sirolimus) inhibits vascular smooth muscle cell DNA synthesis in vitro and suppresses narrowing in arterial allografts and in balloon-injured carotid arteries: Evidence that rapamycin antagonizes growth factor action in immune and nonimmune cells. Transplant Proc 1995;27:430–431. 60. 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. 61. Kornowski R, Hong MK, Ragheb AO, et al. Slow-release taxol coated GR-II stents reduce neointimal formation in porcine coronary instent restenosis model (Abstr). Circulation 1997;96(Suppl I):341. 62. Marx SO, Andrew RM. The development of rapamycin and its application to stent restenosis (editorial). Circulation 2001;104:852–855. 63. Morice MC, Serruys PW, Sousa JE, et al., for the RAVEL study group. A randomized comparison of a sirolimus-eluting stent with a standard stent for coronary revascularization. N Engl J Med 2002;346:1773–1780. 64. Moses JW, Leon MB, Popma JJ, et al., for the SIRIUS Investigators. Sirolimus-eluting stents versus standard stents in patients with stenosis in a native coronary artery. N Engl J Med 2003;349:1315–1323. 65. Kereiakes D, Moses JW, Leon MB, et al. Durable clinical benefit following Cypher coronary stent deployment: SIRIUS study 2-year results (Abstr). Circulation 2003;108(Suppl IV):532. 66. Schofer J, Schlüter M, Gershlick AH, et al., for the E-SIRIUS Investigators. Sirolimus-eluting stents for treatment of patients with long atherosclerotic lesions in small coronary arteries: Double-blind, randomised controlled trial (E-SIRIUS). Lancet 2003;362:1093–1099. 67. Schampaert E, Cohen EA, Schluter M, et al. The Canadian study of the sirolimus-eluting stent in the treatment of patients with long de novo lesions in small native coronary arteries (C-SIRIUS). J Am Coll Cardiol 2004;43:1110–1115. 68. New SIRIUS. Pooled data from E-SIRIUS and C-SIRIUS trials: 8-month angiographic and 9-month clinical follow-ups. Data on file, 2003. Warren, New Jersey: Cordis Corporation. 69. Grube E, Silber SM, Hauptmann KE, et al. TAXUS I: 6- and 12-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. 70. Colombo A, Drzewiecki J, Banning A, et al., for the TAXUS II Study Group. Randomized study to assess the effectiveness of slow- and moderate-release polymer-based paclitaxel-eluting stents for coronary artery lesions. Circulation 2003;108:788–794. 71. Stone GW. TAXUS IV: The pivotal, perspective randomized trial of the slow-rate release polymer-based paclitaxel-eluting TAXUS™ stent. Presented at Transcatheter Cardiovascular Therapeutics, Washington D.C., 2003. 72. Gershlick AH, De Scheerder I, Chevalier B, et al. Inhibition of restenosis with a paclitaxel-eluting polymer-free coronary stent. The European Evaluation of Paclitaxel-Eluting Stent (ELUTES) trial. Circulation 2004;109:487–493. 73. Park SJ, Shim WH, Ho DS, et al. A paclitaxel-eluting stent for the prevention of coronary restenosis. N Engl J Med 2003;348:1537–1545. 74. O'Neill WW. The DELIVER Trial: a randomized comparison of paclitaxel-coated versus metallic stents for treatment of coronary lesions. Presented at: Annual Scientific Session of the American College of Cardiology; Chicago, IL: 2003. 75. Weisz G, Moses JW, Popma JJ, et al. Do overlapping multiple sirolimus-eluting stents impact angiographic and clinical outcomes? Insights from the SIRIUS trial (Abstr). J Am Coll Cardiol 2003;41:33A. 76. Farb A, Heller PF, Shroff S, et al. Pathological analysis of local delivery of paclitaxel via a polymer-coated stent. Circulation 2001;104:473–479. 77. Lincoff AM, Furst JG, Ellis SG, et al. Sustained local delivery of dexamethasone by a novel intravascular eluting stent to prevent restenosis in the porcine coronary injury model. J Am Coll Cardiol 1997;29:808–816. 78. Zidar J, Lincoff AM, Stack R. Biodegradable stents. In: Topol EJ (ed). Textbook of Interventional Cardiology, Second Edition. Philadelphia, PA: W.B. Saunders, 1994: pp. 787–802. 79. Van der Giessen WJ, Lincoff AM, Schwartz RS, et al. Marked inflammatory sequelae to implantation of biodegradable and nonbiodegradable polymers in porcine coronary artery. Circulation 1996;94:1690–1697. 80. Murphy JG, Schwartz RS, Edwards WD, et al. Percutaneous polymeric stents in porcine coronary arteries. Circulation 1992;86:1596–1604. 81. Honda Y, Grube E, de la Fuente L, et al. Novel drug-delivery stent: Intravascular ultrasound observations from the first human experience with the QP2-eluting polymer stent system. Circulation 2001;104:380–383. 82. Degertekin M, Serruys PW, Tanabe K, et al. Long-term follow-up of incomplete stent apposition in patients who received sirolimus-eluting stent for de novo coronary lesions. An intravascular ultrasound analysis. Circulation 2003;108:2747–2750. 83. Leon MB, Moses JW, Popma JJ, et al. A multicenter randomized clinical study of the sirolimus-eluting stent in native coronary lesions: Angiographic results (Abstr). Circulation 2002;106(Suppl II):393.