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DOI: 10.1055/s-0037-1615577
Prevention of Restenosis after Percutaneous Coronary Interventions: The Medical Approach
Publication History
Publication Date:
14 December 2017 (online)
![](https://www.thieme-connect.de/media/10.1055-s-00035024/1999S01/lookinside/thumbnails/10-1055-s-0037-1615577-1.jpg)
Summary
Restenosis following successful percutaneous coronary revascularization continues to represent a major problem limiting the clinical efficacy of this procedure. The underlying mechanisms of restenosis are comprised of a combination of effects from vessel recoil, negative vascular remodeling, thrombus formation and neointimal hyperplasia. Indeed, there are important interactions among all of these mechanisms. For example, neointimal hyperplasia is stimulated by growth factors, which are released by local thrombi and the injured arterial segment itself, and act to enhance the expression of other growth-regulating proteins, in particular “second messengers“, proto-oncogenes and other cell cycle controlling proteins. This results in an inflammatory and myofibroproliferative response, which may worsen vessel narrowing caused by recoil and result in the formation of a clinically significant restenotic lesion.
A multitude of pharmacologic trials have been conducted in an attempt to prevent restenosis, but most have demonstrated little benefit. Studies in smaller numbers of patients have suggested a potential benefit for several classes of agents, including: 1) the antiproliferatives, angiopeptin, trapidil and tranilast; 2) selective elimination or alteration of proliferating cells; 3) enhancement of natural growth inhibitors; and 4) signal transduction blockade or inhibition of the gene expression for various growth-stimulating proteins. Finally, there have been advances in related areas, including development of antithrombotic catheters, novel polymers, and more efficient methods for transferring genes into the vessel wall. All of these offer the possibility of delivering agents (drugs, genes, or antisense oligonucleotides) locally at the site of intervention in a way that may optimize antiproliferative effects while minimizing systemic effects – ultimately leading to a more specific inhibition of the restenosis process.
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References
- 1 Topol EJ, Leya F, Pinkerton CA. et al. on behalf of the CAVEAT study group. A comparison of directional atherectomy with coronary angioplasty in patients with coronary artery disease. N Engl J Med 1993; 329: 221-7.
- 2 Weintraub WS, Boccuzzi SJ, Klein JL. et al. Lack of effect of lovastatin on restenosis after coronary angioplasty. N Engl J Med 1994; 331: 1331-7.
- 3 Eeckhout E, Kappenberger L, Goy JL. Stents for intracoronary placement: current status and future directions. J Am Coll Cardiol 1996; 27: 757-65.
- 4 Belli G, Ellis SG, Topol EJ. Stenting for ischemic heart disease. Progr Cardiovasc Dis 1997; 40: 159-82.
- 5 Foley DP, Serruys PW. Coronary Stenting. Semin Interv Cardiol 1996; 1: 231-2.
- 6 DiMario C, Airoldi F, Reimers B. et al. Bifurcational stenting. Semin Interv Cardiol 1998; 3: 65-76.
- 7 Savage MP, Douglas Jr. JS, Fischman DL. at al for the Saphenous Vein De Novo Trial Investigators Stent placement compared with balloon angioplasty for obstructed coronary bypass grafts. N Engl J Med 1997; 337: 740-77.
- 8 Ellis SG, Savage M, Fischman D. et al. Restenosis after placement of Palmaz-Schatz stent in native coronary arteries. Initial results of a multi-center experience. Circulation 1992; 86: 1836-44.
- 9 De Gregorio J, Kobayashi Y, Albiero R. et al. Coronary artery stenting in the elderly: short-term outcome and long-term angiographic and clinical follow-up. J Am Coll Cardiol 1998; 32: 577-83.
- 10 Carrozza Jr. JP, Kunz RE, Fishman RF, Baim DS. Restenosis after arterial injury caused by coronary stenting in patients with diabetes mellitus. Ann Int Med 1993; 118: 344-9.
- 11 Abizaid A, Kornowski R, Mintz GS. et al. The influence of diabetes mellitus on acute and late clinical outcomes following coronary stent implantation. J Am Coll Cardiol 1998; 32: 584-9.
- 12 Califf RM. Restenosis: the cost to society. Am Heart J 1995; 130: 680-4.
- 13 Hillegass WB, Ohman EM, Califf RM. Restenosis: the clinical issues. In: Textbook of interventional cardiology. Topol EJ, ed. Philadelphia: Saunders 1994; pp 415-35.
- 14 Mintz GS, Popma JJ, Pichard AD. et al. Arterial remodeling after coronary angioplasty: a serial intravascular ultrasound study. Circulation 1996; 94: 35-43.
- 15 Hoffmann R, Mintz GS, Dussaillant GR. et al. Patterns and mechanisms of in-stent restenosis: a serial intravascular ultrasound study. Circulation 1996; 94: 1247-54.
- 16 Komatsu R, Ueda M, Naruko T, Kojima A, Becker AE. Neointimal tissue response at sites of coronary stenting in humans: macroscopic, histological, and immunohistochemical analyses. Circulation 1998; 98: 224-33.
- 17 Fukami MH, Salganicoff L. Human platelet storage organelles. A review. Thromb Haemost 1977; 38: 963-70.
- 18 Fingerle J, Johnson R, Clowes AW. et al. Role of platelets in smooth muscle cell proliferation and migration after vascular injury in rat carotid artery. Proc Natl Acad Sci USA 1989; 86: 8412-6.
- 19 Weiss HJ, Hawiger J, Ruggeri ZM. et al. Fibrinogen-independent platelet adhesion and thrombus formation on subendothelium mediated by glycoprotein IIb-IIIa complex at high shear rate. J Clin Invest 1989; 83: 288-97.
- 20 Le Breton H, Plow EF, Topol EJ. Role of platelets in restenosis after percutaneous coronary revascularization. J Am Coll Cardiol 1996; 28: 1643-51.
- 21 McNamara CA, Sarembock IJ, Gimple LW, Fenton 2d JW, Coughlin SR, Owens GK. Thrombin stimulates proliferation of cultured rat aortic smooth muscle cells by a proteolytically activated receptor. J Clin Invest 1993; 91: 94-8.
- 22 Sugama Y, Malik AB. Thrombin receptor 14-amino acid peptide mediates endothelial hyperadhesivity and neutrophil adhesion by P-selectin-dependent mechanism. Circ Res 1992; 71: 1015-9.
- 23 Lindner V, Reidy MA. Expression of basic fibroblast growth factor and its receptor by smooth muscle cells and endothelium in injured rat arteries: An en-face study. Circ Res 1993; 73: 589-95.
- 24 Shimokawa H, Ito A, Fukumoto Y. et al. Chronic treatment with interleukin-1 beta induces coronary intimal lesions and vasospastic responses in pigs in vivo. The role of platelet-derived growth factor. J Clin Invest 1996; 97: 769-76.
- 25 Muller DW. The role of proto-oncogenes in coronary restenosis. Progr Cardiovasc Dis 1997; 40: 117-28.
- 26 Lefkovits J, Topol EJ. Pharmacological approaches for the prevention of restenosis after percutaneous coronary intervention. Prog Cardiovasc Dis 1997; 40 (2) 141-58.
- 27 Bauters C, Meurice T, Hamon M, McFadden E, Lablanche JM, Bertrand ME. Mechanisms and prevention of restenosis: from experimental models to clinical practice. Cardiovasc Res 1996; 31: 835-46.
- 28 Mak KH, Topol EJ. Clinical trials to prevent restenosis after percutaneous coronary revascularization. Ann N Y Acad Sci 1997; 811: 255-88.
- 29 Landzberg BR, Frishman WH, Lerrick K. Pathophysiology and pharmacological approaches for prevention of coronary artery restenosis following coronary artery ballooon angioplasty and related procedures. Progr Cardiovasc Dis 1997; 39: 361-98.
- 30 Matsuno H, Stassen JM, Vermylen J, Deckmyn H. Inhibition of integrin function by a cyclic RGD-containing peptide prevents neointima formation. Circulation 1994; 90: 2203-6.
- 31 Choi ET, Engel L, Callow AD. et al. Inhibition of neointimal hyperplasia by blocking avP3 integrin with a small peptide antagonist GpenGRGDSPCA. J Vasc Surg 1994; 19: 125-34.
- 32 Bauters C, Isner JM. The biology of restenosis. Progr Cardiovasc Dis 1997; 40: 107-16.
- 33 The EPIC investigators. Use of a monoclonal antibody directed against the platelet glycoprotein IIb/IIIa receptor in high-risk coronary angioplasty. N Engl J Med 1994; 330: 956-61.
- 34 Lincoff AM, Tcheng JE, Ellis SG. et al. IMPACT II investigators. Randomized trial of platelet glycoprotein IIb/IIIa inhibition with Integrelin for prevention of restenosis following coronary intervention. The IMPACT II angiographic substudy. Circulation 1995; 92: I-607.
- 35 The CAPTURE investigators. Randomised placebo-controlled trial of abciximab before and during coronary intervention in refractory unstable angina: The CAPTURE study. Lancet 1997; 349: 1429-35.
- 36 The RESTORE investigators. Effects of platelet glycoprotein IIb/IIIa blockade with tirofiban on adverse cardiac events in patients with unstable angina or acute myocardial infarction undergoing coronary angioplasty. Circulation 1997; 96: 1445-53.
- 37 The EPILOG investigators. Platelet glycoprotein IIb/IIIa receptor blockade and low-dose heparin during percutaneous coronary revascularization. N Engl J Med 1997; 336: 1689-96.
- 38 Moliterno DJ, Topol EJ. Restenosis. Epidemiology and treatment. In: Textbook of Cardiovascular Medicine. Topol EJ. eds. Philadelphia, PA: Lippincott-Raven; 1998. pp 2065-100.
- 39 Serruys PW, Herman JP, Simon R. et al. Helvetica Investigators. A comparison of hirudin with heparin in the prevention of restenosis after coronary angioplasty. N Engl J Med 1995; 333: 757-63.
- 40 Kamikubo Y, Nakahara Y, Takemoto S, Hamuro T, Miyamoto S, Funatsu A. Human recombinant tissue-factor pathway inhibitor prevents the proliferation of cultured human neonatal aortic smooth muscle cells. FEBS Lett 1997; 40 (1) 116-20.
- 41 Vahanian A, Lung B. Role of calcium channel blockers in reducing acute ischaemia and preventing restenosis in PTCA. Drugs 1996; 52: 9-16.
- 42 Hillegass WB, Ohman EM, Leimburger JD, Califf RM. A meta-analysis of randomized trials of calcium antagonists to reduce restenosis after coronary angioplasty. Am J Cardiol 1994; 73: 835-9.
- 43 Radomski MW, Palmer RM, Moncada S. An L-arginine/nitric oxide pathway present in human platelets regulates aggregation. Proc Natl Acad Sci USA 1990; 87: 5190-7.
- 44 Garg UC, Hassid A. Nitric oxide-generating vasodilators and 8-bromocyclic guanosine monophosphate inhibit mitogenesis and proliferation of cultured rat vascular smooth muscle cells. J Clin Invest 1989; 83: 1774-7.
- 45 Varenne O, Pislaru S, Gillijns H, Van Pelt N, Gerard RD, Zoldhelyi P, Van de Werf F, Collen D, Janssens SP. Local adenovirus-mediated transfer of human endothelial nitric oxide synthase reduces luminal narrowing after coronary angioplasty in pigs. Circulation 1998; 98: 919-26.
- 46 Janssens S, Flaherty D, Nong Z, Varenne O. et al. Human endothelial nitric oxide synthase gene transfer inhibits vascular smooth muscle cell proliferation and neointima formation after balloon injury in rats. Circulation 1998; 97: 1274-81.
- 47 Lablanche JM, Grollier G, Lusson JR. et al. Effect of the direct nitric oxide donors linsidomine and molsidomine on angiographic restenosis after coronary balloon angioplasty. The ACCORD Study. Circulation 1997; 95: 83-9.
- 48 Godfried SL, Deckelbaum LI. Natural antioxidants and restenosis after percutaneous transluminal coronary angioplasty. Am Heart J 1995; 129: 203-10.
- 49 Tardif JC, Cote G, Lesperance J, Bourassa M, Lambert J, Doucet S, Bilodeau L, Nattel S, de Guise P. Probucol and multivitamins in the prevention of restenosis after coronary angioplasty. Multivitamins and probucol study group. N Engl J Med 1997; 337: 365-72.
- 50 Yokoi H, Daida H, Kuwabara Y. et al. Effectiveness of an antioxidant in preventing restenosis after percutaneous transluminal coronary angioplasty: the Probucol Angioplasty Restenosis Trial (PART). J Am Coll Cardiol 1997; 30: 855-62.
- 51 Ruef J, Meshel AS, Hu Z, Horaist C, Ballinger CA, Thompson LJ, Subbarao VD, Dumont JA, Patterson C. Flavopiridol inhibits smooth muscle cell proliferation in vitro and neointimal formation in vivo after carotid injury in the rat. Circulation 1999; 100: 659-65.
- 52 Okamoto S, Inden M, Setsuda M. et al. Effects of trapidil (triazolopyrimidine), a platelet-derived growth factor antagonist, in preventing restenosis after percutaneous transluminal coronary angioplasty. Am Heart J 1992; 123: 1439-44.
- 53 Maresta A, Balducelli M, Cantini L. et al. for the STARC investigators Trapidil (triazolopyrimidine), a platelet-derived growth factor antagonist, reduces restenosis after percutaneous transluminal angioplasty. Results of the randomized, double blind STARC study. Circulation 1994; 90: 2710-5.
- 54 Kosuga K, Tamai H, Ueda K, Hsu YS. et al. The effectiveness of tranilast on restenosis after directional coronary atherectomy. Am Heart J 1997; 134: 712-8.
- 55 Fingerle J, Faulmuller A, Muller G. et al. Pituitary factors in blood plasma are ncessary for smooth muscle cell proliferation in response to injury in vivo. Arterios Thrombo 1992; 12: 1488-95.
- 56 Eriksen UH, Amtorp O, Bagger JP. et al. Randomized double blind Scandinavian trial of angiopeptin versus placebo for the prevention of clinical events and restenosis after coronary balloon angioplasty. Am Heart J 1995; 130: 1-8.
- 57 Emanuelsson H, Beatt KJ, Bagger JP. et al. for the European Angiopeptin Study Group Long-term effects of angiopeptin treatment in coronary angioplasty. Reduction of clinical events but not angiographic restenosis. Circulation 1995; 91: 1689-96.
- 58 Bailey SR. Local drug delivery: current applications. Progr Cardiovasc Dis 1997; 40: 183-204.
- 59 Kostopulos KG, Wang K, De Scheerder I. Local drug delivery with stents. In: Frontiers in interventional cardiology. Beyar R, Keren G, Leon MB, Serruys PW. eds. St. Louis, Missouri: Mosby; 1997. pp 183-92.
- 60 Serruys PW, Emanuelsson H, van der, Giessen W. et al. Heparin-coated Palmaz-Schatz stents in human coronary arteries. Early outcomes of the Benestent-II pilot study. Circulation 1996; 93: 412-22.
- 61 Aggarwal RK, Ireland DC, Azrin MA. et al. Antithrombotic potential of polymer-coated stents eluting platelet glycoprotein IIb/IIIa receptor antibody. Circulation 1996; 94: 3311-7.
- 62 Flugelman MY, Weisz A, Keren-Tal I, Halon DA, Lewis BS. Genetic engineering of stents. In: Frontiers in interventional cardiology. Beyar R, Keren G, Leon MB, Serruys PW. eds. St. Louis, Missouri: Mosby; 1997. pp 217-20.
- 63 Feldman LJ, Tahlil O, Steg G. Perspectives of arterial gene therapy for the prevention of restenosis. Cardiovasc Res 1996; 32 (2) 194-207.
- 64 Feldman LJ, Riessen R, Steg PG. Prevention of restenosis after coronary angioplasty: towards a molecular approach?. Fundam Clin Pharmacol 1995; 9 (1) 8-16.
- 65 Kutryk MJB, Serruys PW, Bruining N, SabatÈ M, Ligthart J, van den Brand M, Hamburger JN, van der Giessen WJ, Foley DP, de Feyter PJ. Randomized trial of antisense oligonucleotide against c-myc for the prevention of restenosis after stenting: results of the Thoraxcenter “ITALICS” trial. Eur Heart J. 1998 19. 569.