The authors discuss the mechanism of action, clinical trial data, and economic impact of both the paclitaxel and sirolimus drug eluting stents (DESs). Both DESs have been approved by the Food and Drug Administration for the treatment of native coronary arteries to prevent in-stent restenosis (ISR), which patients have experienced since the advent of balloon angioplasty and the bare metal stent. In-stent restenosis, which manifests itself as ischemic symptoms in patients, occurs as a result of the healing process after stent implantation. Until now, there has not been an effective method to prevent ISR. The sirolimus and paclitaxel DESs elute agents that act locally by different mechanisms to reduce neointimal hyperplasia, which is primarily responsible for ISR. Both DESs are capable of reducing the rate of ISR. There are certain physical and mechanistic differences between the 2 stents; the stents have not been compared head to head. Currently, they are indicated for uncomplicated native coronary lesions. Further investigation is needed to define their roles in the treatment of more complex lesions.
Sousa JE, Serruys PW, Costa MA. New frontiers in cardiology. Drug-eluting stents: part I. Circulation. 2003;107:2274-2279.
4.
Sigwart U, Puel J, Mirkovitch V, Joffre F, Kappenberger L.Intravascular stents to prevent occlusion and restenosis after transluminal angioplasty. N Eng J Med. 1987;316(12):701-706.
5.
Fischman D, Leon M, Baim D, et al. A randomized comparison of coronary stent placement and balloon angioplasty in the treatment of coronary artery disease. Stent Restenosis Study Investigators. N Eng J Med. 1994;334:491-501.
6.
Serruys P, de Jaegere P, Kiemeneij F, et al. A comparison of balloon-expandable-stent implantation with balloon angioplasty in patients with coronary artery disease. Benestent Study Group. N Eng J Med. 1994;331:489-495.
7.
Serruys PW, Strauss BH, van Beusekom HM, van der Giessen WJ. Stenting of coronary arteries: has a modern Pandora’s box been opened?J Am Coll Cardiol. 1991;17(6 suppl B):143B-154B.
8.
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 Eng J Med. 1998;339:1665-1671.
Rensing BJ, Hermans WR, Strauss BH, Serruys PW. Regional differences in elastic recoil after percutaneous transluminal coronary angioplasty: a quantitative angiographic study. J Am Coll Cardiol. 1991;17(suppl):34B-38B.
11.
Ip JH, Fuster V, Badimon L, et al. Syndromes of accelerated atherosclerosis: role of vascular injury and smooth muscle cell proliferation. J Am Coll Cardiol. 1990;15:1667-1687.
12.
Mizuno O, Ikeda U, Hojo Y, et al. Tissue factor expression in coronary circulation as a prognostic factor for late restenosis after coronary angioplasty. Cardiology. 2001;95:84-89.
13.
Marso SP, Lincoff AM, Ellis SG, et al. Optimizing the percutaneous interventional outcomes for patients with diabetes mellitus: results of the EPISTENT diabetic substudy. Circulation. 1999;100:2477-2484.
14.
Leon MB, Bakhai A.Drug-eluting stents and glycoprotein IIb/IIIa inhibitors: combination therapy for the future. Am Heart J. 2003;146:S13-S17.
15.
Glagov S, Weisenberg E, Zarins CK, et al. Compensatory enlargement of human atherosclerotic coronary arteries. N Eng J Med. 1987;316:1371-1375.
16.
Post MJ, de Smet BJ, van der Helm Y, et al. Arterial remodeling after balloon angioplasty or stenting in an atherosclerotic experimental model. Circulation. 1997;96:996-1003.
Ryan ST, Koteliansky VE, Gotwals PJ, Lindner V.Transforming growth factor-beta-dependent events in vascular remodeling following arterial injury. J Vasc Res. 2003;40(1):37-46.
19.
Ward MR, Agrotis A, Kanellakis P, Hall J, Jennings G, Bobik A.Tranilast prevents activation of transforming growth factor-beta system, leukocyte accumulation, and neointimal growth in porcine coronary arteries after stenting. Arterioscler Thromb Vasc Biol. 2002;22:940-948.
20.
Mintz GS, Kent KM, Pichard AD, et al. Intravascular ultrasound insights into mechanisms of stenosis formation and restenosis. Cardiol Clin. 1997;15:17-29.
21.
Hoffman R, Mintz GS, Dussaillant GR, et al. Patterns and mechanisms of in-stent restenosis: a serial intravascular ultrasound study. Circulation. 1996;94:1247-1254.
22.
Shi Y, O’brien JE, Fard A, et al. Adventitial myofibroblasts contribute to neointimal formation in injured porcine coronary arteries. Circulation. 1996;94:1655-1664.
23.
Bauters C, Isner JM. The biology of restenosis. In: Topol EJ, ed. Textbook of Cardiovascular Medicine. Philadelphia, Pa: Lippincott-Raven; 1998:2465-2490.
24.
Deuel TF, Bianchi C, Cantley L.Restenosis injury: a problem in regulation of growth. In: Chien KR. Molecular Basis of Cardiovascular Disease: A Companion to Braunwald’s Heart Disease. Philadelphia, Pa: WB Saunders Co; 1998:367-386.
25.
Carter AJ. TOR of the cell cycle: are there important implications for diabetics in the era of the drug-eluting stent?Catheter Cardiovasc Interv. 2004;61:233-236.
26.
Sanz-Gonzalez SM, Poch E, Perez-Roger I, et al. Control of vascular smooth muscle cell growth by cyclin-dependent kinase inhibitory proteins and its implications in cardiovascular disease. Front Biosci. 2000;5:D619-D628.
27.
Ekholm SV, Reed SI. Regulation of G(1) cyclin-dependent kinases in the mammalian cell cycle. Curr Opin Cell Biol. 2000;12:676-684.
28.
Okamoto E, Couse T, De Leon H, et al. Perivascular inflammation after balloon angioplasty of porcine coronary arteries. Circulation. 2001;104:2228-2235.
29.
Bertrand O, Sipehia R, Mongrain R, et al. Biocompatibility aspects of new stent technology. J Am Coll Cardiol. 1998;32:562-571.
30.
Gunn J, Cumberland D.Stent coatings and local drug delivery. Eur Heart J. 1999;20:1693-1700.
31.
Peng T, Gibula P, Yao K, Goosen MFA. Role of polymers in improving the results of stenting in coronary arteries. Biomaterials. 1996;17:685-694.
32.
Leon MB, Abizaid A, Moses JW. The CYPHER Stent: A New Gold Standard in the Treatment of Coronary Artery Disease. The CYPHER Stent Monograph. Miami Lakes, Fla: Cordis Corporation, a Johnson & Johnson Company.
33.
Sousa JE, Serruys PW, Costa MA. New frontiers in cardiology. Drug-eluting stents: part I. Circulation. 2003;107:2274-2279.
34.
Sousa JE, Serruys PW, Costa MA. New frontiers in cardiology. Drug-eluting stents: part II. Circulation. 2003;107:2283-2289.
35.
Hwang CW, Wu D, Edelman ER. Physiological transport forces govern drug distribution for stent-based delivery. Circulation. 2001;104(5):600-605.
36.
Sehgal SN. Sirolimus: its discovery, biological properties, and mechanism of action. Transplant Proc. 2003;35(3 suppl):7S-14S.
37.
Huang S, Bjornsti M, Houghton PJ. Rapamycins: mechanism of action and cellular resistance. Cancer Biol Ther. 2003;2(3):222-232.
38.
Marx SO, Marks AR. Bench to bedside: the development of rapamycin and its application to stent restenosis. Circulation. 2001;104:852-855.
39.
Poon M, Marx SO, Gallo R, et al. Rapamycin inhibits vascular smooth muscle cell migration. J Clin Invest. 1996;98:2277-2283.
40.
Saunders RN, Metcalfe MS, Nicholson ML. Rapamycin in transplantation: a review of the evidence. Kidney Int. 2001;51:3-16.
41.
Shiff PB, Fan J, Horwitz SB. Promotion of microtubule assembly in vitro by Taxol. Nature. 1979;277:665-667.
42.
Rowinsky EK, Cazenave LA, Donehower RC. Taxol: a novel investigational antimicrotubule agent. J Natl Cancer Inst. 1990;82:1247-1259.
Axel DI, Kunert W, Goggelmann C, et al. Paclitaxel inhibits arterial smooth muscle cell proliferation and migration in vitro and in vivo using local drug delivery. Circulation. 1997;96:636-645.
46.
Sousa JE, Costa MA, Abizaid AC, et al. Sustained suppression of neointimal proliferation by sirolimus-eluting stents: one-year angiographic and intravascular ultrasound follow-up. Circulation. 2001;104:2007-2011.
47.
Sousa JE, Costa MA, Sousa A, et al. Two-year angiographic and intravascular ultrasound follow-up after implantation of sirolimus-eluting stents in human coronary arteries. Circulation. 2003;107:381-383.
48.
Degertekin M, Serruys PW, Foley DP, et al. Persistent inhibition of neointimal hyperplasia after sirolimus-eluting stent implantation: long term (up to 2 years) clinical, angiographic, and intravascular ultrasound follow-up. Circulation. 2002;106:1610-1613.
49.
Sousa JE, Abizaid A, Costa MA, et al. Late four-year follow-up from the First-in-Man experience after implantation of sirolimus-eluting stents. Presented at: American College of Cardiology Annual Scientific Session 2004; March 10, 2004; New Orleans, La.
50.
Morice M, Serruys PW, Sousa JE, et al. A randomized comparison of a sirolimus-eluting stent with a standard stent for coronary revascularization. N Engl J Med. 2002;346:1773-1780.
51.
Morice MC, Serruys PW, Constantini C, et al. Three-year follow-up of RAVEL: a randomized study with the sirolimus-eluting Bx velocity stent in the treatment of patients with de novo native coronary artery lesions [abstract]. Presented at: American College of Cardiology Annual Scientific Session 2004; March 10, 2004; New Orleans, La.
52.
Moses JW, Leon MB, Popma JJ, et al. Sirolimus-eluting stents versus standard stents in patients with stenosis in a native coronary artery. N Eng J Med. 2003;349:1315-1323.
53.
Schofer J, Schluter M, Gershlick AH, et al. Sirolimus-eluting stents for treatment of patients with long atherosclerotic lesions in small coronary arteries: double-blind, randomized controlled trial (E-SIRIUS). Lancet. 2003;362:1093-1099.
54.
Park S, Shim WH, Ho DS, et al. A paclitaxel-eluting stent for the prevention of coronary restenosis. N Engl J Med. 2003;348:1537-1545.
55.
Lansky AJ, Costa RA, Mintz GS, et al. Non–polymer-based paclitaxel-coated coronary stents for the treatment of patients with de novo coronary lesions: angiographic follow-up of the DELIVER clinical trial. Circulation. 2004;109:1948-1954.
56.
Gershlick A, 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.
57.
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.
58.
Columbo A, Drzewiecki J, Banning A, et al. TAXUS II: 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.
59.
Tanabe K, Serruys PW, Grube E, et al. TAXUS III Trial: in-stent restenosis treated with stent-based delivery of paclitaxel incorporated in a slow-release polymer formulation. Circulation. 2003;107(4):559-564.
60.
Stone GW, Ellis SG, Cox DA, et al. TAXUS IV: a polymer-based, paclitaxel-eluting stent in patients with coronary artery disease. N Eng J Med. 2004;350:221-231.
61.
Cohen DJ, Bakhai A, Shi C, et al. Cost-effectiveness of sirolimus drug-eluting stents for the treatment of complex coronary stenoses: results from the randomized SIRIUS trial. J Am Coll Cardiol. 2003;41(1 suppl):32A-32A.
62.
Lacey MJ, Clark MA, Halpern MT, et al. Estimated cost-effectiveness of the TAXUS paclitaxel-eluting coronary stent [abstract]. Am J Cardiol. 2003;92:26L-26L.
63.
Cohen DJ, Mahoney E, Lavelle TA, et al. Cost effectiveness of the TAXUS paclitaxel eluting coronary stent system [abstract]. Presented at: American College of Cardiology Annual Scientific Session 2004; March 10, 2004; New Orleans, La.
64.
Virmani R, Liistro F, Stankovic G, et al. Mechanism of late instent restenosis after implementation of a paclitaxel derivateeluting polymer stent system in humans. Circulation. 2002;106:2649-2651.
65.
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:r38-r42.
66.
Jeremias A.Sylvia B, Bridges J, et al. Stent thrombosis after successful sirolimus-eluting stent implantation. Circulation. 2004;109(16):1930-1930.
67.
Colombo A, Moses JW, Morice MC, et al. Randomized study to evaluate sirolimus-eluting stents implanted at coronary bifurcation lesions. Circulation. 2004;109:1244-1249.
68.
Regar E, Serruys PW, Bode C, et al. Angiographic findings of the multicenter randomized study with the sirolimus-eluting Bx velocity balloon-expandable stent (RAVEL): sirolimus-eluting stents inhibit restenosis irrespective of the vessel size. Circulation. 2002;106:1949-1956.
69.
Saia F, Lemos PA, Sianos G, et al. Effectiveness of sirolimuseluting stent implantation for recurrent in-stent restenosis after brachytherapy. Am J Cardiol. 2003;92:200-203.
70.
Radke PW, Kobella S, Kaiser A, et al. Treatment of in-stent restenosis using a paclitaxel-eluting stent: acute results and long-term follow-up of a matched-pair comparison with intracoronary beta-radiation therapy. Eur Heart J. 2004;25:920-925.
71.
Saia F, Lemos PA, Lee C, et al. Sirolimus-eluting stent implantation in ST-elevation acute myocardial infarction: a clinical and angiographic study. Circulation. 2003;108:1927-1929.
72.
Lemos PA, Saia F, Hofma SH, et al. Short- and long-term clinical benefit of sirolimus eluting stents compared to conventional bare stents for patients with acute myocardial infarction. J Am Coll Cardiol. 2004;43:704-708.
73.
Hodgson JM, Bottner RK, Klein LW, et al. Drug-eluting stent task force: final report and recommendations of the working committees on cost-effectiveness/economics, access to care, and medicolegal issues. Catheter Cardiovasc Interv. 2004;62:1-17.
74.
Curfman GD. Sirolimus-eluting coronary stents. N Engl J Med. 2002;346:1770-1771.
