The Utility of Animal Models in the Preclinical Study of Interventions to Prevent Human Coronary Artery Restenosis: Analysis and Recommendations

G. J. Johnson; T. R. Griggs; L. Badimon

doi:10.1055/s-0037-1614578

Thrombosis and Haemostasis, Table of Contents

Thromb Haemost 1999; 81(05): 835-843.
DOI: 10.1055/s-0037-1614578

Scientific and Standardization Committee Communication

Schattauer GmbH

The Utility of Animal Models in the Preclinical Study of Interventions to Prevent Human Coronary Artery Restenosis: Analysis and Recommendations

On behalf of the Subcommittee on Animal, Cellular and Molecular Models of Thrombosis and Haemostasis of the Scientific and Standardization Committee of the International Society on Thrombosis and Haemostasis

G. J. Johnson

,

T. R. Griggs

¹From the VA Medical Center and University of Minnesota, Minneapolis, USA, University of North Carolina, Chapel Hill, USA

,

L. Badimon

²Cardiovascular Research Center, IIBB(CSIC)-HSCSP-UAB, Barcelona, Spain

› Author Affiliations

Abstract

Summary

Small animal models have several advantageous characteristics, but those used in preclinical restenosis research have lacked efficacy in predicting the success of interventions to inhibit restenosis in humans.

Large animal models have been more successful than small animal models in predicting efficacy of interventions to inhibit restenosis in humans, but the results of studies carried out with these models have not been uniformly predictive.

Confirmation of the results of small animal studies in large animals has not always yielded information predictive of success in humans; however, the absence of such confirmation has had strong negative predictive value.

Small animal models used for evaluation of interventions to inhibit luminal narrowing following arterial instrumentation have failed to closely simulate human atherosclerosis and the stenotic lesions subjected to instrumentation in humans.

Transgenic, atherosclerotic animals hold promise for the development of more useful small animal models to study mechanisms of the response of diseased arteries to angioplasty and stents.

The pig has been the most useful large animal to study stenosis/ restenosis, but more information is needed to overcome the limitations of this model.

Full Text

References

References
1 Landzberg BR, Frishman WH, Lerrick K. Pathophysiology and pharmacological approaches for prevention of coronary artery restenosis following coronary artery balloon angioplasty and related procedures.. Prog Cardiovasc Dis 1997; 39: 361-98.
2 Serruys PW, de Jaegere P, Kiemeneij F, Macaya C, Rutsch W, Heyndrickx G, Emanuelsson H, Marco J, Legrand V, Materne P, Belardi J, Sigwart U, Colombo A, Goy JJ, van den Heuvel P, Delcan J, Morel M-A. 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:: 489-95.
3 Fischman DL, Leon MB, Baim DS, Schatz RA, Savage MP, Penn I, Detre K, Veltri L, Ricci D, Nobuyoshi M, Cleman M, Heuser R, Almond D, Teirstein PS, Fish RD, Colombo A, Brinker J, Moses J, Shaknovich A, Hirshfeld J, Bailey S, Ellis S, Rake R, Goldberg S. 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.
4 Belli G, Ellis SG, Topol EJ. Stenting for ischemic heart disease.. Prog Cardiovasc Dis 1997; 40: 159-82.
5 Antoniucci D, Valenti R, Santoro GM, Bolognese L, Trapani M, Cerisano G, Boddi V, Fazzini PF. Restenosis after coronary stenting in current clinical practice.. Am Heart J 1998; 135: 510-8.
6 Lefkovits J, Topol EJ. Pharmacological approaches for the prevention of restenosis after percutaneous coronary intervention.. Prog Cardiovasc Dis 1997; 40: 141-58.
7 Badimon L.. Models to study thrombotic disorders.. Thromb Haemost 1997; 78:: 667-71.
8 Handley DA. Experimental therapeutics and clinical studies in (re)stenosis.. Micron 1995; 26: 51-68.
9 Topol EJ. Restenosis: introduction.. Prog Cardiovasc Dis 1997; 40: 95-6.
10 Schwartz RS, Murphy JG, Edwards WD, Camrud AR, Vlietstra RE, Holmes DR. Restenosis after balloon angioplasty. A practical proliferative model in porcine coronary arteries.. Circulation 1990; 82: 2190-200.
11 Schwartz RS, Holmes DR. Pigs, dogs, baboons, and man: lessons for stenting from animal studies.. J Interven Cardiol 1994; 7: 355-68.
12 Geary RL, Adams MR, Benjamin ME, Williams JK. Conjugated equine estrogens inhibit progression of atherosclerosis but have no effect on intimal hyperplasia or arterial remodeling induced by balloon catheter injury in monkeys.. J Am Coll Cardiol 1998; 31: 1158-64.
13 Hanson SR, Powell JS, Dodson T, Lumsden A, Kelly AB, Anderson JS, Clowes AW, Harker LA. Effects of angiotensin converting enzyme inhibition with cilazapril on intimal hyperplasia in injured arteries and vascular grafts in the baboon.. Hypertension 1991; 18 II (suppl) II-70-II-6.
14 Buchwald AB, Unterberg C, Nebendahl K, Gröne H-J, Wiegand V. Low-molecular-weight heparin reduces neointimal proliferation after coronary stent implantation in hypercholesterolemic minipigs.. Circulation 1992; 86: 531-7.
15 Banning A, Brewer L, Wendt M, Groves PH, Cheadle H, Penny WJ, Crawford N. Local delivery of platelets with encapsulated iloprost to balloon injured pig carotid arteries: effect on platelet deposition and neointima formation.. Thromb Haemost 1997; 77: 190-6.
16 Clopath P. The effect of acetylsalicylic acid (asa) on the development of atherosclerotic lesions in miniature swine.. Br J Exp Path 1980; 61: 440-3.
17 Unterberg C, Sandrock D, Nebendahl K, Buchwald AB. Reduced acute thrombus formation results in decreased neointimal proliferation after coronary angioplasty.. J Am Coll Cardiol 1995; 26: 1747-54.
18 Abendschein DR, Recchia D, Meng YY, Oltrona L, Wickline SA, Eisen-berg PR. Inhibition of thrombin attenuates stenosis after arterial injury in minipigs.. J Am Coll Cardiol 1996; 28: 1849-55.
19 Gallo R, Padurean A, Toschi V, Bichler J, Fallon JT, Chesebro JH, Fuster V, Badimon JJ. Prolonged thrombin inhibition reduces restenosis after balloon angioplasty in porcine coronary arteries.. Circulation 1998; 97: 581-8.
20 Geary RL, Koyama N, Wang TW, Vergel S, Clowes AW. Failure of heparin to inhibit intimal hyperplasia in injured baboon arteries. The role of heparin-sensitive and -insensitive pathways in the stimulation of smooth muscle cell migration and proliferation.. Circulation 1995; 91: 2972-81.
21 Lablanche J-M, McFadden EP, Meneveau N, Lusson JR, Bertrand B, Metzger J-P, Legrand V, Grollier G, Macaya C, de Bruyne B, Vahanian A, Grentzinger A, Masquet C, Wolf J-E, Tobelem G, Fontecave S, Vacheron A, d’Azemar P, Bertrand ME. Effect of nadroparin, a low-molecular-weight heparin, on clinical and angiographic restenosis after coronary balloon angioplasty. The FACT study.. Circulation 1997; 96: 3396-402.
22 Faxon DP, Spiro TE, Minor S, Coté G, Douglas J, Gottlieb R, Califf R, Dorosti K, Topol E, Gordon JB, Ohmen M. and the ERA Investigators. Low molecular weight heparin in prevention of restenosis after angioplasty.. Results of enoxaparin restenosis (ERA) trial. Circulation 1994; 90: 908-14.
23 Gerdes C, Faber-Steinfeld V, Yalkinoglu O, Wohlfeil S. Comparison of the effects of the thrombin inhibitor r-hirudin in four animal models of neointima formation after arterial injury.. Arterioscler Thromb Vasc Biol 1996; 16: 1306-11.
24 The MERCATOR Study Group. Does the new angiotensin converting enzyme inhibitor cilazapril prevent restenosis after percutaneous transluminal coronary angioplasty? Results of the MERCATOR study: a multicenter, randomized, double-blind placebo-controlled trial.. Circulation 1992; 86:: 100-10.
25 Faxon DP. on behalf of the MARCATOR Study Group. Effect of high dose angiotensin-convering enzyme inhibition on restenosis: final results of the MARCATOR study, a multicenter double-blind, placebo-controlled trial of cilazapril.. J Am Coll Cardiol 1995; 25:: 362-9.
26 Pratt RE, Dzau VJ. Pharmacological strategies to prevent restenosis. Lessons learned from blockade of the renin-angiotensin system.. Circulation 1996; 93: 848-52.
27 Yamabe T, Imazu M, Yamamoto H, Ueda H, Hattori Y, Hayashi Y, Sekiguchi Y, Ito M, Yamakido M. Effect of cilazapril on vascular restensosis after percutaneous transluminal coronary angioplasty.. Coronary Artery Dis 1995; 6: 573-9.
28 Lam JYT, Lacoste L, Bourassa MG. Cilazapril and early atherosclerotic changes after balloon injury of porcine carotid arteries.. Circulation 1992; 85: 1542-7.
29 Huber KC, Schwartz RS, Edwards WD, Camrud AR, Bailey KR, Jorgenson MA, Holmes Jr DR. Effects of angiotensin converting enzyme inhibition on neointimal proliferation in a porcine coronary injury model.. Am Heart J 1993; 125: 695-701.
30 Kim S, Kawamura M, Wanibuchi H, Ohta K, Hamaguchi A, Omura T, Yukimura T, Miura K, Iwao H.. Angiotensin II type 1 receptor blockade inhibits the expression of immediate-early genes and fibronectin in rat injured artery.. Circulation 1995; 92: 88-95.
31 Huckle WR, Drag MD, Acker WR, Powers M, McFall RC, Holder DJ, Fujita T, Stabilito II, Kim D, Ondeyka DL, Mantlo NB, Chang RSL, Reilly CF, Schwartz RS, Greenlee WJ, Johnson Jr RG. Effects of subtype-selective and balanced angiotensin II receptor antagonists in a porcine coronary artery model of vascular restenosis.. Circulation 1996; 93: 1009-19.
32 Matsumoto Y, Tani T, Watanabe K, Kimura Y. Effects of cilostazol, an antiplatelet drug, on smooth muscle cell proliferation after endothelial denudation in rats.. Jap J Pharmacol 1992; 58 I (supplement) 284P (abstract).
33 Kubota Y, Kichikawa K, Uchida H, Maeda M, Nishimine K, Makutani S, Sakaguchi S, Yoshioka T, Ohishi H, Kimura Y, Yoshikawa T. Pharmaco-logic treatment of intimal hyperplasia after metallic stent placement in the peripheral arteries. An experimental study.. Invest Radiol 1995; 30: 532-7.
34 Tsuchikane E, Katoh O, Sumitsuji S, Fukuhara A, Funamoto M, Otsuji S, Tateyama H, Awata N, Kobayashi T. Impact of cilostazol on intimal proliferation after directional coronary atherectomy.. Am Heart J 1998; 135: 495-502.
35 Keiser JA, Uprichard ACG. Restenosis: is there a pharmacologic fix in the pipeline?. Adv Pharmacol 1997; 39: 313-51.
36 Baek S, March KL. Gene therapy for restenosis. Getting nearer the heart of the matter.. Circ Res 1998; 82: 295-305.
37 Bauters C, Isner JM. The biology of restenosis.. Prog Cardiovasc Dis 1997; 40: 107-16.
38 Currier JW, Faxon DP. Restenosis after percutaneous transluminal coronary angioplasty: have we been aiming at the wrong target?. J Am Coll Cardiol 1995; 25: 516-20.
39 Chien KR. Genes and physiology: molecular physiology in genetically engineered animals.. J Clin Invest 1996; 98 supplement S19-S26.
40 Plump A. Atherosclerosis and the mouse: a decade of experience.. Ann Med 1997; 29: 193-8.
41 Topouzis S, Majesky MW. Smooth muscle lineage diversity in the chick embryo. Two types of aortic smooth muscle cell differ in growth and receptor-mediated transcriptional responses to transforming growth factor-beta.. Dev Biol 1996; 178: 430-45.
42 Majesky MW, Dong XR, Topouzis S. Smooth muscle cell diversity and the extracellular matrix in a rat model of restenosis.. P R Health Sci J 1996; 15: 187-91.
43 Yang Z, Oemar BS, Carrel T, Kipfer B, Julmy F, Lüscher TF. Different proliferative properties of smooth muscle cells of human arterial and venous bypass vessels. Role of PDGF receptors, mitogen-activated protein kinase, and cyclin-dependent kinase inhibitors.. Circulation 1998; 97: 181-7.
44 Badimon JJ, Fernandez-Ortiz A, Meyer B, Mailhac A, Fallon JT, Falk E, Badimon L, Fuster V, Chesebro JH. Different response to balloon angioplasty of carotid and coronary arteries: effects on acute platelet disposition and intimal thickening.. Atherosclerosis 1998; 140: 307-14.
45 Schwartz RS. Pathophysiology of restenosis: interaction of thrombosis, hyperplasia, and/or remodeling.. Am J Cardiol 1998; 81: 14E-7E.
46 de Smet BJGL, Pasterkamp G, van der Helm YJ, Borst C, Post MJ. The relation between de novo atherosclerosis remodeling and angioplasty-induced remodeling in an atherosclerotic yucatan micropig model.. Arterioscler Thromb Vasc Biol 1998; 18: 702-7.
47 Kakuta T, Currier JW, Haudenschild CC, Ryan TJ, Faxon DP. Differences in compensatory vessel enlargement, not intimal formation, account for restenosis after angioplasty in the hypercholesterolemic rabbit model.. Circulation 1994; 89: 2809-15.
48 Staab ME, Srivatsa SS, Lerman A, Sangiorgi G, Jeong MH, Edwards WD, Holmes Jr DR, Schwartz RS. Arterial remodeling after experimental percutaneous injury is highly dependent on advential injury and histopathology.. International J Cardiol 1997; 58: 31-40.
49 Gross DR. Thromboembolic phenomena and the use of the pig as an appropriate animal model for research on cardiovascular devices.. International J Artificial Organs 1997; 20: 195-203.
50 Serruys PW, Herrman J-PR, Simon R, Rutsch W, Bode C, Laarman G-J, van DijK R, van den Bos AA, Umans VAWM, Fox KAA, Close P, Deckers JW. for the Helvetica Investigators. A comparison of hirudin with heparin in the prevention of restenosis after coronary angioplasty.. N Engl J Med 1995; 333:: 757-63.
51 Clarkson TB, Prichard RW, Morgan TM, Petrick GS, Klein KP. Remodeling of coronary arteries in human and nonhuman primates.. JAMA 1994; 271: 289-94.
52 Strong JP, Bhattacharyya AK, Eggen DA, Stary HC, Malcom GT, New-man III WP, Restrepo C. Long-term induction and regression of diet-induced atherosclerotic lesions in rhesus monkeys. II. Morphometric evaluation of lesions by light microscopy in coronary and carotid arteries.. Arterioscler Thromb 1994; 14: 2007-16.
53 Fincham JE, Benade AJS, Kroger M, Smuts CM, Gobregts E, Chalton DO, Kritchevsky D. Atherosclerosis: aortic lipid changes induced by diets suggest diffuse disease with focal severity in primates that model human atheromas.. Nutrition 1998; 14: 17-22.
54 Geary RL, Williams JK, Golden D, Brown DG, Benjamin ME, Adams MR. Time course of cellular proliferation, intimal hyperplasia, and remodeling following angioplasty in monkeys with established atherosclerosis. A nonhuman primate model of restenosis.. Aterioscler Thromb Vasc Biol 1996; 16: 34-43.
55 Mondy JS, Williams JK, Adams MR, Dean RH, Geary RL. Structural determinants of lumen narrowing after angioplasty in atherosclerotic nonhuman primates.. J Vasc Surg 1997; 26: 875-83.
56 Willerson JT, Yao S-K, McNatt J, Benedict CR, Anderson HV, Golino P, Murphree SS, Buja LM. Frequency and severity of cyclic flow alternations and platelet aggregation predict the severity of neointimal proliferation following experimental coronary stenosis and endothelial injury.. Proc Natl Acad Sci USA 1991; 88: 10624-8.
57 Schwartz RS, Edwards WD, Bailey KR, Camrud AR, Jorgenson MA, Holmes Jr DR. Differential neointimal response to coronary artery injury in pigs and dogs. Implications for restenosis models.. Arterioscler Thromb 1994; 14: 395-400.
58 Kikuchi S, Umemura K, Kondo K, Saniabadi AR, Nakashima M. Photochemically induced endothelial injury in the mouse as a screening model for inhibitors of vascular intimal thickening.. Arterioscler Thromb Vasc Biol 1998; 18: 1069-78.
59 Braun-Dullaeus RC, Mann MJ, Dzau VJ. Cell cycle progression. New therapeutic target for vascular proliferative disease.. Circulation 1998; 98: 82-9.
60 Gershlick AH, Baron J. Dealing with in-stent restenosis.. Heart 1998; 79: 319-23.
61 Clowes AW, Karnowsky MJ. Suppression by heparin of smooth muscle cell proliferation in injured arteries.. Nature 1977; 265: 625-6.
62 Guyton JR, Rosenberg RD, Clowes AW, Karnovsky MJ. Inhibition of rat arterial smooth muscle cell proliferation by heparin. In vivo studies with anticoagulant and nonanticoagulant heparin.. Circ Res 1980; 46: 625-34.
63 Clowes AW, Clowes MM. Kinetics of cellular proliferation after arterial injury. II. Inhibition of smooth muscle growth by heparin.. Lab Invest 1985; 52: 611-6.
64 Okada T, Bark DH, Mayberg MR. Localized release of perivascular heparin inhibits intimal proliferation after endothelial injury without systemic anticoagulation.. Neurosurgery 1989; 25: 892-8.
65 Edelman ER, Adams DH, Karnovsky MJ. Effect of controlled adventitial heparin delivery on smooth muscle cell proliferation following endothelial injury.. Proc Natl Acad Sci USA 1990; 87: 3773-7.
66 Clowes AW, Clowes MM, Vergel SC, Müller RKM, Powell JS, Hefti F, Baumgartner HR. Heparin and cilazapril together inhibit injury-induced intimal hyperplasia.. Hypertension 1991; 18 II (suppl) II65-II9.
67 Gimple LW, Gertz SD, Haber HL, Ragosta M, Powers ER, Roberts WC, Sarembock IJ. Effect of chronic subcutaneous or intramural administration of heparin on femoral artery restenosis after balloon angioplasty in hyper-cholesterolemic rabbits. A quantitative angiographic and histopathological study.. Circulation 1992; 86: 1536-46.
68 Rogers C, Welt FGP, Karnovsky MJ, Edelman ER. Monocyte recruitment and neointimal hyperplasia in rabbits. Coupled inhibitory effects of heparin.. Arterioscler Thromb Vasc Biol 1996; 16: 1312-8.
69 Ellis SG, Roubin GS, Wilentz J, Douglas Jr JS, King III SB. Effect of 18- to 24-hour heparin administration for prevention of restenosis after uncomplicated coronary angioplasty.. Am Heart J 1989; 117: 777-82.
70 Berk BC, Gordon JB, Alexander RW. Pharmacologic roles of heparin and glucocorticoids to prevent restenosis after coronary angioplasty.. J Am Coll Cardiol 1991; 17: 111B-7B.
71 Hanke H, Oberhoff M, Hanke S, Hassenstein S, Kamenz J, Schmid KM, Betz E, Karsch KR. Inhibition of cellular proliferation after experimental balloon angioplasty by low-molecular-weight heparin.. Circulation 1992; 85: 1548-56.
72 Currier JW, Pow TK, Haudenschild CC, Minihan AC, Faxon DP. Low molecular weight heparin (enoxaparin) reduces restenosis after iliac angioplasty in the hypercholesterolemic rabbit.. J Am Coll Cardiol 1991; 17: 118B-25B.
73 Singh JP, Rothfuss KJ, Wiernicki TR, Lacefield WB, Kurtz WL, Brown RF, Brune KA, Bailey D, Dube GP. Dipyridamole directly inhibits vascular smooth muscle cell proliferation in vitro and in vivo: implications in the treatment of restenosis after angioplasty.. J Am Coll Cardiol 1994; 23: 665-71.
74 Faxon DP, Sanborn TA, Haudenschild CC, Ryan TJ. Effect of antiplatelet therapy on restenosis after experimental angioplasty.. Am J Cardiol 1984; 53: 72C-6C.
75 Radic ZS, O’Malley MK, Mikat EM, Makhoul RG, McCann RL, Cole CW, Hagen P-O.. The role of aspirin and dipyridamole on vascular DNA synthesis and intimal hyperplasia following deendothelialization.. J Surg Res 1986; 41:: 84-91.
76 Schwartz L, Bourassa MG, Lespérance J, Aldridge HE, Kazim F, Salvatori VA, Henderson M, Bonan R, David PR. Aspirin and dipyridamole in the prevention of restenosis after percutaneous transluminal coronary angioplasty.. New Eng J Med 1988; 318: 1714-9.
77 Schwartz L, Lesperance J, Bourassa MG, Eastwood C, Kazim F, Arafah M, Ganassin L. The role of antiplatelet agents in modifying the extent of restenosis following percutaneous transluminal coronary angioplasty.. Am Heart J 1990; 119: 232-6.
78 White CW, Chaitman B, Knudtson ML, Chisholm RJ. and the Ticlopidine Study Group. Antiplatelet agents are effective in reducing the acute ischemic complications of angioplasty but do not prevent restenosis: results from the ticlopidine trial.. Coronary Artery Disease 1991; 2:: 757-67.
79 Okamoto S, Inden M, Setsuda M, Konishi T, Nakano T. 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.
80 Reece AH, Walton PL. Inhibition of intimal proliferation of rabbit aorta by ticlopidine.. Thromb Haemost 1979; 42: 367 (abstract).
81 Kastrati A, Schühlen H, Hausleiter J, Walter H, Zitzmann-Roth E, Hadamitzky M, Elezi S, Ulm K, Dirschinger J, Neumann F-J, Schömig A. Restenosis after coronary stent placement and randomization to a 4-week combined antiplatelet or anticoagulant therapy. Six-month angiographic follow-up of the intracoronary stenting and antithrombotic regimen (ISAR) trial.. Circulation 1997; 96: 462-7.
82 Isogaya M, Yamada N, Koike H, Ueno Y, Kumagai H, Ochi Y, Okazaki S, Nishio S. Inhibition of restenosis by beraprost sodium (a prostaglandin I₂analogue) in the atherosclerotic rabbit artery after angioplasty.. J Cardiovasc Pharmacol 1995; 25: 947-52.
83 Knudtson ML, Flintoft VF, Roth DL, Hansen JL, Duff HJ. Effect of short-term prostacyclin administration on restenosis after percutaneous transluminal coronary angioplasty.. J Am Coll Cardiol 1990; 15: 691-7.
84 Gershlick AH, Spriggins D, Davies SW, Syndercombe Court YD, Timmins J, Timmis AD, Rothman MT, Layton C, Balcon R. Failure of epoprostenol (prostacyclin, PGI₂) to inhibit platelet aggregation and to prevent restenosis after coronary angioplasty: results of a randomized placebo controlled trial.. Br Heart J 1994; 71: 7-15.
85 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.
86 Azrin MA, Ling FS, Chen Q, Pawashe A, Migliaccio F, Homer R, Todd M, Ezekowitz MD. Preparation, characterization, and evaluation of a monoclonal antibody against the rabbit platelet glycoprotein IIb/IIIa in an experimental angioplasty model.. Circ Res 1994; 75: 268-77.
87 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.
88 Topol EJ, Califf RM, Weisman HF, Ellis SG, Tcheng JE, Worley S, Ivan-hoe R, George BS, Fintel D, Weston M, Sigmon K, Anderson KM, Lee KL, Willerson JT. on behalf of the EPIC investigators. Randomized trial of coronary intervention with antibody against platelet IIb/IIIa integrin for reduction of clinical restenosis: results at six months.. Lancet 1994; 343:: 881-6.
89 Topol EJ, Ferguson JJ, Weisman HF, Tcheng JE, Ellis SG, Kleiman NS, Ivanhoe RJ, Wang AL, Miller DP, Anderson KM, Califf RM. for the EPIC Investigator Group. Long-term protection from myocardial ischemic events in a randomized trial of brief integrin α₃blockade with percutaneous coronary intervention.. JAMA 1997; 278:: 479-84.
90 The EPILOG Investigators. Platelet glycoprotein IIb/IIIa receptor blockade and low-dose heparin during percutaneous coronary revascularization.. N Eng J Med 1997; 336:: 1689-96.
91 Lincoff AM, Califf RM, Anderson KM, Weisman HF, Aguirre FV, Klei-man NS, Harrington RA, Topol EJ. for the EPIC Investigators. Evidence for prevention of death and myocardial infarction with platelet membrane glycoprotein IIb/IIIa receptor blockade by abciximab (c7E3 Fab) among patients with unstable angina undergoing percutaneous coronary revascularization.. J Am Coll Cardiol 1997; 30:: 149-56.
92 The CAPTURE Investigators. Randomized placebo-controlled trial of abciximab before and during coronary intervention in refractory unstable angina: the CAPTURE study.. Lancet 1997; 349:: 1429-35.
93 The IMPACT-II Investigators. Randomised placebo-controlled trial of effect of eptifibatide on complications of percutaneous coronary intervention: IMPACT-II.. Lancet 1997; 349:: 1422-8.
94 Gibson CM, Goel M, Cohen DJ, Piana RN, Deckelbaum LI, Harris KE, King II, SB I. for the Restore Investigators. Six-month angiographic and clinical follow-up of patients prospectively randomized to receive either tirofiban or placebo during angioplasty in the restore trial.. J Am Coll Cardiol 1998; 32:: 28-34.
95 Powell JS, Muller RKM, Baumgartner HR. Suppression of the vascular response to injury: the role of angiotensin-converting enzyme inhibitors.. J Am Coll Cardiol 1991; 17: 137B-42B.
96 Thornton MA, Gruentzig AR, Hollman J, King III SB, Douglas JS. Coumadin and aspirin in prevention of recurrence after transluminal coronary angioplasty: a randomized study.. Circulation 1984; 69: 721-7.
97 Taylor RR, Gibbons FA, Cope GD, Cumpston GN, Mews GC, Luke P. Effects of low-dose aspirin on restenosis after coronary angioplasty.. Am J Cardiol 1991; 68: 874-8.
98 Savage MP, Goldberg S, Bove AA, Deutsch E, Vetrovec G, Macdonald RG, Bass T, Margolis JR, Whitworth HB, Taussig A, Hirshfeld JW, Cowley M, Hill JA, Marks RG, Fischman DL, Handberg E, Herrmann H, Pepine CJ. for the M-HEART II Study Group. Effect of thromboxane A₂blockade on clinical outcome and restenosis after successful coronary angioplasty. Multi-hospital eastern atlantic restenosis tial (M-Heart II).. Circulation 1995; 92:: 3194-200.
99 Serruys PW, Rutsch W, Heyndrickx GR, Danchin N, Gijs Mast E, Wijns W, Rensing BJ, Vos J, Stibbe J. for the Coronary Artery Restenosis Prevention on Repeated Thromboxane-Antagonism Study Group (CARPORT). Prevention of restenosis after percutaneous transluminal coronary angioplasty with thromboxane A₂-receptor blockade. A randomized, double-blind, placebo-controlled trial.. Circulation 1991; 84:: 1568-80.
100 Handley DA, Van Valen RG, Melden MK, Saunders RN. Suppression of rat carotid lesion development by the calcium channel blocker PN 200-110. Am J Pathol 1986; 124: 88-93.
101 Powell JS, Clozel J-P, Müller RKM, Kuhn H, Hefti F, Hosang M, Baumgartner HR. Inhibitors of angiotensin-converting enzyme prevent myointimal proliferation after vascular injury.. Science 1989; 245: 186-8.
102 Cook NS, Zerwes H-G, Pally C, Rudin M, Hof RP. Decreased lumen size after balloon injury despite inhibition of neointimal thickening and anti-vasospastic treatment.. Cardiovasc Res 1994; 28: 215-20.
103 Corcos T, David PR, Val PG, Renkin J, Dangoisse V, Rapold HG, Bourassa MG. Failure of diltiazem to prevent restenosis after percutaneous trans-luminal coronary angioplasty.. Am Heart J 1985; 109: 926-31.
104 Whitworth HB, Roubin GS, Hollman J, Meier B, Leimgruber PP, Douglas Jr JS, King II, SB I, Gruentzig AR. Effect of nifedipine on recurrent stenosis after percutaneous transluminal coronary angioplasty.. J Am Coll Cardiol 1986; 8: 1271-6.
105 Stone GW, Rutherford BD, McConahay DR, Johnson WL, Giorgi LV, Ligon RW, Hartzler GO. A randomized trial of corticosteroids for the prevention of restenosis in 102 patients undergoing repeat coronary angioplasty.. Cathet Cardiovasc Diagn 1989; 18: 227-31.
106 Pepine CJ, Hirshfeld JW, Macdonald RG, Henderson MA, Bass TA, Goldberg S, Savage MP, Vetrovec G, Cowley M, Taussig AS, Whitworth HB, Margolis JR, Hill JA, Bove AA, Jugo R. for the M-HEART Group. A controlled trial of corticosteroids to prevent restenosis after coronary angioplasty.. Circulation 1990; 81:: 1753-61.
107 Farhy RD, Carretero OA, Ho K-L, Scicli AG. Role of kinins and nitric oxide in the effects of angiotensin converting enzyme inhibitors on neointima formation.. Circ Res 1993; 72: 1202-10.
108 Miyauchi K, Kawai S, Okada R, Yamaguchi H. Limitations of angioten-sin-converting enzyme inhibitor in restenosis of a deep arterial injury model.. Jpn Circ J 1998; 62: 53-60.
109 Shibutani T, Kanda A, Ishigai Y, Mori T, Chiba K, Tanaka M, Tachizawa H. Inhibitory effect of perindopril, a novel angiotensin-converting enzyme inhibitor, on neointima formation after balloon injury in rats and cholesterol-fed rabbits.. J Cardiovasc Pharmacol 1994; 24: 509-16.
110 Osterrieder W, Müller RKM, Powell JS, Clozel J-P, Hefti F, Baumgartner HR. Role of angiotensin II in injury-induced neointima formation in rats.. Hypertension 1991; 18 II (suppl) II-60-II-4.
111 Kawamura M, Terashita Z-I, Okuda H, Imura Y, Shino A, Nakao M, Nishikawa K. TCV-116, a novel angiotensin II receptor antagonist, prevents intimal thickening and impairment of vascular function after carotid injury in rats.. J Pharmacol Exp Ther 1993; 266: 1664-9.
112 Clozel J-P, Hess P, Michael C, Schietinger K, Baumgartner HR.. Inhibition of converting enzyme and neointima formation after vascular injury in rabbits and guinea pigs.. Hypertension 1991; 18 II (suppl) II-55-II-9.
113 Eckardt H, Völker W, Brüning T, Faber V, Buddecke E. Lovastatin reduces myointimal proliferation after vascular injury.. Eur Heart J 1991; 12 (Suppl) 9 (abstract).
114 Gellman J, Ezekowitz MD, Sarembock IJ, Azrin MA, Nochomowitz LE, Lerner E, Haudenschild CC. Effect of lovastatin on intimal hyperplasia after balloon angioplasty: a study in an atherosclerotic hypercholesterolemic rabbit.. J Am Coll Cardiol 1991; 17: 251-9.
115 Sahni R, Maniet AR, Voci G, Banka VS. Prevention of restenosis by lovastatin after successful coronary angioplasty.. Am Heart J 1991; 121: 1600-8.
116 Weintraub WS, Boccuzzi SJ, Klein JL, Kosinski AS, King II, SB I, Ivanhoe R, Cedarholm JC, Stillabower ME, Talley JD, DeMaio SJ, O’Neill WW, Frazier II JE, Cohen-Bernstein CL, Robbins DC, Brown III CL, Alexander RW. and the Lovastatin Restenosis Trial Study Group. Lack of effect of lovastatin on restenosis after coronary angioplasty.. New Eng J Med 1994; 331:: 1331-7.
117 Cody RJ. Results from late breaking clinical trials sessions at ACC ’97.. J Am Coll Cardiol 1997; 30: 1-7.
118 Bertrand ME, McFadden EP, Fruchart J-C, van Belle E, Commeau P, Grollier G, Bassand J-P, Machecourt J, Cassagnes J, Mossard J-M, Vacheron A, Castaigne A, Danchin N, Lablanche J-M. for the PREDICT Trial Investigators. Effect of pravastatin on angiographic restenosis after coronary balloon angioplasty.. J Am Coll Cardiol 1997; 30:: 863-9.
119 Sarembock IJ, Gertz SD, Gimple LW, Owen RM, Powers ER, Roberts WC. Effectiveness of recombinant desulphatohirudin in reducing restenosis after balloon angioplasty of atherosclerotic femoral arteries in rabbits.. Circulation 1991; 84: 232-43.
120 Ragosta M, Barry WL, Gimple LW, Gertz SD, McCoy KW, Stouffer GA, McNamara CA, Powers ER, Owens GK, Sarembock IJ. Effect of thrombin inhibition with desulfatohirudin on early kinetics of cellular proliferation after balloon angioplasty in atherosclerotic rabbits.. Circulation 1996; 93: 1194-200.
121 Jang Y, Guzman LA, Lincoff AM, Gottsauner-Wolf M, Forudi F, Hart CE, Courtman DW, Ezban M, Ellis SG, Topol EJ. Influence of blockade at specific levels of the coagulation cascade on restenosis in a rabbit atherosclerotic femoral artery injury model.. Circulation 1995; 92: 3041-50.
122 Lundergan CF, Foegh ML, Ramwell PW. Peptide inhibition of myointimal proliferation by angiopeptin, a somatostatin analogue.. J Am Coll Cardiol 1991; 17: 132B-6B.
123 Conte JV, Foegh ML, Calcagno D, Wallace RB, Ramwell PW. Peptide inhibition of myointimal proliferation following angioplasty in rabbits.. Transplant Proc 1989; 21: 3686-8.
124 Howell MH, Adams MM, Wolfe MS, Foegh ML, Ramwell PW.. Angiopeptin inhibition of myointimal hyperplasia after balloon angioplasty of large arteries in hypercholesterolaemic rabbits.. Clin Sci 1993; 85:: 183-8.
125 Hong MK, Bhatti T, Matthews BJ, Stark KS, Cathapermal SS, Foegh ML, Ramwell PW, Kent KM. The effect of porous infusion balloon-delivered angiopeptin on myointimal hyperplasia after balloon injury in the rabbit.. Circulation 1993; 88: 638-48.
126 Santoian EC, Schneider JE, Gravanis MB, Foegh M, Tarazona N, Cipolla GD, King III SB. Angiopeptin inhibits intimal hyperplasia after angioplasty in porcine coronary arteries.. Circulation 1993; 88: 11-4.
127 Emanuelsson H, Beatt KJ, Bagger J-P, Balcon R, Heikkilä J, Piessens J, Schaeffer M, Suryapranata H, Foegh M. 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.
128 von Essen R, Ostermaier R, Grube E, Mäurer W, Tebbe U, Erbel R, Roth M, Oel W, Brom J, Weidinger G. for the VERAS Investigators. Effects of octreotide treatment on restenosis after coronary angioplasty. Results of the VERAS study.. Circulation 1997; 96:: 1482-7.
129 Chen S-J, Chen Y-F, Miller DM, Li H, Oparil S. Mithramycin inhibits myointimal proliferation after balloon injury of the rat carotid artery in vivo.. Circulation 1994; 90: 2468-73.
130 Sollott SJ, Cheng L, Pauly RR, Jenkins GM, Monticone RE, Kuzuya M, Froehlich JP, Crow MT, Lakatta EG, Rowinsky EK, Kinsella JL. Taxol inhibits neointimal smooth muscle cell accumulation after angioplasty in the rat.. J Clin Invest 1995; 95: 1869-76.
131 Axel DI, Kunert W, Göggelmann C, Oberhoff M, Herdeg C, Küttner A, Wild DH, Brehm BR, Riessen R, Köveker G, Karsch KR. Paclitaxel inhibits arterial smooth muscle cell proliferation and migration in vitro and in vivo using local drug delivery.. Circulation 1997; 96: 636-45.
132 Muller DWM, Ellis SG, Topol EJ. Colchicine and antineoplastic therapy for the prevention of restenosis after percutaneous coronary interventions.. J Am Coll Cardiol 1991; 17: 126B-31B.
133 Banai S, Wolf Y, Golomb G, Pearle A, Waltenberger J, Fishbein I, Schneider A, Gazit A, Perez L, Huber R, Lzarovichi G, Rabinovich L, Levitzki A, Gert SD. PDGF-receptor tyrosine kinase blocker AG1295 selectively attenuates smooth muscle cell growth in vitro and reduces neointimal formation after balloon angioplasty in swine.. Circulation 1998; 97: 1960-9.
134 O’Keefe Jr JH, McCallister BD, Bateman TM, Kuhnlein DL, Ligon RW, Hartzler GO. Ineffectiveness of colchicine for the prevention of restenosis after coronary angioplasty.. J Am Coll Cardiol 1992; 19: 1597-600.
135 Verin V, Popowski Y, Urban P, Belenger J, Redard M, Costa M, Widmer M-C, Rouzaud M, Nouet P, Grob E, Schwager M, Kurtz JM, Rutishauser W. Intra-arterial beta irradiation prevents neointimal hyperplasia in a hypercholesterolemic rabbit restenosis model.. Circulation 1995; 92: 2284-90.
136 Hehrlein C, Gollan C, Dönges K, Metz J, Riessen R, Fehsenfeld P, von Hodenberg E, Kübler W. Low-dose radioactive endovascular stents prevent smooth muscle cell proliferation and neointimal hyperplasia in rabbits.. Circulation 1995; 92: 1570-5.
137 Wiederman JG, Marboe C, Amols H, Schwartz A, Weinberger J. Intracoronary irradiation markedly reduces neointimal proliferation after balloon angioplasty in swine: persistent benefit at 6-month follow-up.. J Am Coll Cardiol 1995; 25: 1451-6.
138 Waksman R, Robinson KA, Crocker IR, Wang C, Gravanis MB, Cipolla GD, Hillstead RA, King II, SB I. Intracoronary low-dose α-irradiation inhibits neointima formation after coronary artery balloon injury in the swine restenosis model.. Circulation 1995; 92: 3025-31.
139 Carter AJ, Laird JR, Bailey LR, Hoopes TG, Farb A, Fischell DR, Fischell RE, Fischell TA, Virmani R. Effects of endovascular radiation from a α-particle-emitting stent in a porcine coronary restenosis model. A dose-response study.. Circulation 1996; 94: 2364-8.
140 Mazur W, Ali MN, Khan MM, Dabaghi SF, De Felice CA, Paradis Jr P, Butler EB, Wright AE, Fajardolf LF, French BA, Raizner AE. High dose intracoronary radiation for inhibition of neointimal formation in the stented and balloon-injured porcine models of restenosis; angiographic, morphometric, and histopathologic analyses.. Int J Radiat Oncol 1996; 36: 777-88.
141 Teirstein PS, Massullo V, Jani S, Popma JJ, Mintz GS, Russo RJ, Schatz RA, Guarneri EM, Steuterman S, Morris NB, Leon MB, Tripuraneni P. Catheter-based radiotherapy to inhibit restenosis after coronary stenting.. N Engl J Med 1997; 336: 1697-703.
142 Condado JA, Waksman R, Gurdiel O, Espinosa R, Gonzalez J, Burger B, Villoria G, Acquatella H, Crocker IR, Seung KB, Liprie SF. Long-term angiographic and clinical outcome after percutaneous transluminal coronary angioplasty and intracoronary radiation therapy in humans.. Circulation 1997; 96: 727-32.
143 King II, SB I, Williams DO, Chougule P, Klein JL, Waksman R, Hilstead R, Macdonald J, Anderberg K, Crocker IR. Endovascular α-radiation to reduce restenosis after coronary balloon angioplasty. Results of the beta energy restenosis trail (BERT).. Circulation 1998; 97: 2025-30.
144 Tiell ML, Sussman I I, Gordon PB, Saunders RN. Suppression of fibroblast proliferation in vitro and of myointimal hyperplasia in vivo by the triazolopyrimidine, trapidil.. Artery 1983; 12: 33-50.
145 Ohnishi H, Yamaguchi K, Shimada S, Sato M, Funato H, Katsuki Y, Dab-asaki T, Suzuki Y, Saitoh Y, Kumagai A. An evidence for “response to injury” hypothesis.. Life Sci 1982; 31: 2595-602.
146 Lui MW, Roubin GS, Robinson KA, Black JR A, Hearn JA, Siegel RJ, King III SB. Trapidil in preventing restenosis after balloon angioplasty in the atherosclerotic rabbit.. Circulation 1990; 81: 1089-93.
147 Maresta A, Balducelli M, Cantini L, Casari A, Chioin R, Fabbri M, Fontanelli A, Monici Preti PA, Repetto S, De Servi S, Varani E. for the STARC Investigators. Trapidil (triazolopyrimidine), a platelet-derived growth factor antagonist, reduces restenosis after percutaneous transluminal coronary angioplasty. Results of the randomized, double-blind STARC study.. Circulation 1994; 90:: 2710-5.
148 Ferns GAA, Forster L, Stewart-Lee A, Konneh M, Nourooz-Zadeh J, Änggård EE. Probucol inhibits neointimal thickening and macrophage accumulation after balloon injury in the cholesterol-fed rabbit.. Proc Natl Acad Sci USA 1992; 89: 11312-6.
149 Schneider JE, Berk BC, Gravanis MB, Santoian EC, Cipolla GD, Tarazona N, Lessegue B, King II, SB I. Probucol decreases neointimal formation in a swine model of coronary artery balloon injury. A possible role for antioxidants in restenosis.. Circulation 1993; 88: 628-37.
150 Tardif J-C, Côté G, Lespérance J, Bourassa M, Lambert J, Doucet S, Bilodeau L, Nattel S, de Guise P. for the Multivitamins and Probucol Study Group. Probucol and multivitamins in the prevention of restenosis after coronary angioplasty.. N Engl J Med 1997; 337:: 365-72.
151 Yokoi H, Daida H, Kubwabara Y, Nishikawa H, Takatsu F, Tomihara H, Nakata Y, Kutsumi Y, Ohshima S, Nishiyama S, Seki A, Kato K, Nishimura S, Kanoh T, Yamaguchi H. Effectiveness of an antioxidant in preventing restenosis after percutaneous transluminal coronary angioplasty: the probucol angioplasty restenosis trial.. J Am Coll Cardiol 1997; 30: 855-62.
152 Setsuda M, Inden M, Hiraoka N, Okamoto S, Tanaka H, Okinaka T, Nishimura Y, Okano H, Kouji T, Konishi T, Nakano T.. Probucol therapy in the prevention of restenosis after successful percutaneous transluminal coronary angioplasty.. Clin Therapeutics 1993; 15: 374-82.
153 Watanabe K, Sekiya M, Ikeda S, Miyagawa M, Hashida K. Preventive effects of probucol on restenosis after percutaneous transluminal coronary angioplasty.. Am Heart J 1996; 132: 23-9.
154 Rodés J, Côté G, Lespérance J, Bourassa MG, Doucet S, Bilodeau L, Bertrand OF, Harel F, Gallo R, Tardif J-C.. Prevention of restenosis after angioplasty in small coronary arteries with probucol. Circulation 1998; 97:: 429-36.
155 Freyschuss A, Stiko-Rahm A, Swedenborg J, Henriksson P, Björkhem I, Berglund L, Nilsson J. Antioxidant treatment inhibits the development of intimal thickening after balloon injury of the aorta in hypercholesterolemic rabbits.. J Clin Invest 1993; 91: 1282-8.
156 LaFont AM, Chai Y-C, Cornhill JF, Whitlow PL, Howe PH, Chisolm GM. Effect of alpha-tocopherol on restenosis after angioplasty in a model of experimental atherosclerosis.. J Clin Invest 1995; 95: 1018-25.