Top

Published in:

01-06-2012 | Original Paper

Inhibition of neointimal hyperplasia with a novel zotarolimus coated balloon catheter

Authors: Bodo Cremers, John L. Toner, Lewis B. Schwartz, Randolf von Oepen, Ulrich Speck, Nicola Kaufels, Yvonne P. Clever, Dirk Mahnkopf, Michael Böhm, Bruno Scheller

Published in: Clinical Research in Cardiology | Issue 6/2012

Abstract

Background

Non stent based delivery of antiproliferative agents using drug coated balloon catheters may offer additional flexibility and efficacy in a broad range of applications. The lipophilic antiproliferative drug zotarolimus makes it a potential candidate for balloon delivery. The aim of the present study was to evaluate the safety and efficacy of a prototype zotarolimus coated balloon (ZCB) catheter in comparison to a zotarolimus eluting stent (ZES) in the porcine coronary overstretch model.

Methods

Eighty-four stents (diameters 3.0 and 3.5 mm; length 15 mm) were implanted in LAD and Cx of 42 domestic pigs: control (TriMaxx, Abbott, polymer coated stent without drug, implanted with uncoated PCI catheter, n = 56); ZES (ZoMaxx, Abbott, stent coated with zotarolimus in polymer, implanted with uncoated PCI catheter, n = 14); ZCB (TriMaxx, Abbott, polymer coated stent without drug, implanted with zotarolimus coated PCI catheter, n = 14). Drug content of the vessel wall (n = 9) was measured about 10–30 min post intervention with ZCB in additional pigs.

Results

Immediately after ZCB treatment 101 ± 31 μg of zotarolimus was detected in the coronary arteries. After 28 days ZES led to a reduction of neointimal area from 4.32 ± 1.45 to 3.32 ± 1.11 mm² (P = 0.019 vs. control). The effect of neointimal inhibition was more pronounced with the novel ZCB (2.79 ± 1.43 mm², P = 0.001 vs. control). Inflammation score was significantly reduced in vessels treated with the ZCB (0.75 ± 0.86 compared to control (1.45 ± 0.94, P = 0.013) and ZES (1.65 ± 0.90, P = 0.012).

Conclusion

Zotarolimus coated balloons and stents were found to effectively reduce neointimal proliferation in the porcine coronary model. Inflammation scores were significantly reduced after treatment with the coated balloon. Zotarolimus balloon coating might be a novel option in preventing and treating restenosis.

De Labriolle A, Pakala R, Bonello L, Lemesle G, Scheinowitz M, Waksman R (2009) Paclitaxel-eluting balloon: from bench to bed. Catheter Cardiovasc Interv 73:643–652PubMedCrossRef

Waksman R, Pakala R (2009) Drug-eluting balloon: the comeback kid? Circ Cardiovasc Interv 2:352–358PubMedCrossRef

Scheller B, Speck U, Abramjuk C, Bernhardt U, Böhm M, Nickenig G (2004) Paclitaxel balloon coating, a novel method for prevention and therapy of restenosis. Circulation 110:810–814PubMedCrossRef

Cremers B, Biedermann M, Mahnkopf D, Böhm M, Scheller B (2009) Comparison of two different paclitaxel-coated balloon catheters in the porcine coronary restenosis model. Clin Res Cardiol 98:325–330PubMedCrossRef

Speck U, Scheller B, Abramjuk C, Breitwieser C, Dobberstein J, Böhm M, Hamm B (2006) Neointima inhibition: comparison of effectiveness of non-stent-based local drug delivery and a drug-eluting stent in porcine coronary arteries. Radiology 240:411–418PubMedCrossRef

Cremers B, Speck U, Kaufels N, Mahnkopf D, Kühler M, Böhm M, Scheller B (2009) Drug-eluting balloon: very short-term exposure and overlapping. Thromb Haemost 101:201–206PubMed

Scheller B, Hehrlein C, Bocksch W, Rutsch W, Haghi D, Dietz U, Böhm M, Speck U (2006) Treatment of coronary in-stent restenosis with a paclitaxel-coated balloon catheter. N Engl J Med 355:2113–2124PubMedCrossRef

Scheller B, Hehrlein C, Bocksch W, Rutsch W, Haghi D, Dietz U, Böhm M, Speck U (2008) Two year follow-up after treatment of coronary in-stent restenosis with a paclitaxel-coated balloon catheter. Clin Res Cardiol 97:773–781PubMedCrossRef

Unverdorben M, Vallbracht C, Cremers B, Heuer H, Hengstenberg C, Maikowski C, Werner GS, Antoni D, Kleber FX, Bocksch W, Leschke M, Ackermann H, Boxberger M, Speck U, Degenhardt R, Scheller B (2009) Paclitaxel-coated balloon catheter versus paclitaxel-coated stent for the treatment of coronary in-stent restenosis. Circulation 119:2986–2994PubMedCrossRef

10.

Tepe G, Zeller T, Albrecht T, Heller S, Schwarzwälder U, Beregi JP, Claussen CD, Oldenburg A, Scheller B, Speck U (2008) Local delivery of paclitaxel to inhibit restenosis during angioplasty of the leg. N Engl J Med 358:689–699PubMedCrossRef

11.

Werk M, Langner S, Reinkensmeier B, Boettcher HF, Tepe G, Dietz U, Hosten N, Hamm B, Speck U, Ricke J (2008) Inhibition of restenosis in femoropopliteal arteries: paclitaxel-coated versus uncoated balloon: femoral paclitaxel randomized pilot trial. Circulation 118:1358–1365PubMedCrossRef

12.

Garcia-Touchard A, Burke SE, Toner JL, Cromack K, Schwartz RS (2006) Zotarolimus-eluting stents reduce experimental coronary artery neointimal hyperplasia after 4 weeks. Eur Heart J 27:988–993PubMedCrossRef

13.

Abizaid A, Lansky AJ, Fitzgerald PJ, Tanajura LF, Feres F, Staico R, Mattos L, Abizaid A, Chaves A, Centemero M, Sousa AG, Sousa JE, Zaugg MJ, Schwartz LB (2007) Percutaneous coronary revascularization using a trilayer metal phosphorylcholine-coated zotarolimus-eluting stent. Am J Cardiol 99:1403–1408PubMedCrossRef

14.

Lasave LI, Costa Jde R Jr, Abizaid AA, Feres F, Tanajura LF, Staico R, Abizaid AA, Beraldo P, Sousa AM, Sousa JE (2007) A three-dimensional intravascular ultrasound comparison between the new zotarolimus-eluting stent (ZoMaxx) and the non-drug-eluting TriMaxx stent. J Invasive Cardiol 19:303–308

15.

Chevalier B, Di Mario C, Neumann FJ, Ribichini F, Urban P, Popma JJ, Fitzgerald PJ, Cutlip DE, Williams DO, Ormiston J, Grube E, Whitbourn R, Schwartz LB, ZoMaxx I Investigators (2008) A randomized, controlled, multicenter trial to evaluate the safety and efficacy of zotarolimus-versus paclitaxel-eluting stents in de novo occlusive lesions in coronary arteries. The ZoMaxx I trial. JACC Cardiovasc Interv 1:524–532PubMedCrossRef

16.

Cromack KR, Xu X, Peykova D, Palwai S (2005) Physicochemical profiling of drug compounds for drug-eluting stents, ABT-578, rapamycin, paclitaxel, and other drugs. CRT, Abstract 501

17.

Abizaid A, Popma JJ, Tanajura LF, Hattori K, Solberg B, Larracas C, Feres F, Costa Jde R Jr, Schwartz LB (2007) Clinical and angiographic results of percutaneous coronary revascularization using a trilayer stainless steel-tantalum-stainless steel phosphorylcholine-coated stent: the TriMaxx trial. Catheter Cardiovasc Interv 70:914–919

18.

Schwartz RS, Huber KC, Murphy JG, Edwards WD, Camrud AR, Vlietstra RE, Holmes DR (1992) Restenosis and the proportional neointimal response to coronary artery injury: results in a porcine model. J Am Coll Cardiol 19:267–274PubMedCrossRef

19.

Kornowski R, Hong MK, Tio FO, Bramwell O, Wu H, Leon MB (1998) In-stent restenosis: contributions of inflammatory responses and arterial injury to neointimal hyperplasia. J Am Coll Cardiol 31:224–230PubMedCrossRef

20.

Stone GW, Ellis SG, Cox DA, Hermiller J, O’Shaughnessy C, Mann JT, Turco M, Caputo R, Bergin P, Greenberg J, Popma JJ, TAXUS-IV Investigators (2004) A polymer-based, paclitaxel-eluting stent in patients with coronary artery disease. N Engl J Med 350:221–231PubMedCrossRef

21.

Moses JW, Leon MB, Popma JJ, Fitzgerald PJ, Holmes DR, O’Shaughnessy C, Caputo RP, Kereiakes DJ, Williams DO, Teirstein PS, Jaeger JL, SIRIUS Investigators (2003) Sirolimus-eluting stents versus standard stents in patients with stenosis in a native coronary artery. N Engl J Med 349:1315–1323PubMedCrossRef

22.

Serruys PW, Ruygrok P, Neuzner J, Piek JJ, Seth A, Schofer JJ, Richardt G, Wiemer M, Carrié D, Thuesen L, Boone E, Miquel-Herbert K, Daemen J (2006) A randomised comparison of an everolimus-eluting coronary stent with a paclitaxel-eluting coronary stent: the SPIRIT II trial. Eurointervention 2:286–294PubMed

23.

Fajadet J, Wijns W, Laarman G-J, Kuck K-H, Ormiston J, Münzel T, Popma JJ, Fitzgerald PJ, Bonan R, Kuntz RE (2006) Randomized, doubleblind, multicenter study of the Endeavor zotarolimus-eluting phosphorylcholine-encapsulated stent for treatment of native coronary artery lesions: clinical and angiographic results of the Endeavor II trial. Circulation 114:798–806PubMedCrossRef

24.

Windecker S, Serruys PW, Wandel S, Buszman P, Trznadel S, Linke A, Lenk K, Ischinger T, Klauss V, Eberli F, Corti R, Wijns W, Morice MC, di Mario C, Davies S, van Geuns RJ, Eerdmans P, van Es GA, Meier B, Jüni P (2008) Biolimus-eluting stent with biodegradable polymer versus sirolimus-eluting stent with durable polymer for coronary revascularisation (LEADERS): a randomised non-inferiority trial. Lancet 372:1163–1173PubMedCrossRef

25.

Mori T, Kinoshita Y, Watanabe A, Yamaguchi T, Hosokawa K, Honjo H (2006) Retention of paclitaxel in cancer cells for 1 week in vivo and in vitro. Cancer Chemother Pharmacol 58:665–672PubMedCrossRef

26.

Ranade SV, Miller KM, Richard RE, Chan AK, Allen MJ, Helmus NM (2004) Physical characterization of controlled release of paclitaxel from Taxus™Express²™ drug-eluting stent. J Biomed Mater Res 71A:625–634CrossRef

27.

Burke SE, Kuntz RE, Schwartz LB (2006) Zotarolimus (ABT-578) eluting stents. Adv Drug Deliv Rev 58:437–446PubMedCrossRef

28.

Schwartz RS, Edelman E, Virmani R, Carter A, Granada JF, Kaluza GL, Chronos NAF, Robinson KA, Waksman R, Weinberger J, Wilson GJ, Wilensky RL (2008) Drug-eluting stents in preclinical studies Update consensus recommendations for preclinical evaluation. Circ Cardiovasc Interv 1:143–153PubMedCrossRef

29.

DuVall M, Qin JI, Clifford A, Barry CM, Nowak SA, Sabaj KM, Zielinski DA, Smits G, Zhang J, Cromack K, Dube H, Schwartz LB, Krasula RW (2004) ABT-578 elution profile and arterial penetration using the ZOMAXX drug-eluting stent. Am J Cardiol 94:6E

30.

Speck U, Scheller B, Abramjuk C, Grossmann S, Mahnkopf D, Simon O (2004) Inhibition of restenosis in stented porcine coronary arteries: uptake of Paclitaxel from angiographic contrast media. Invest Radiol 39:182–186PubMedCrossRef

Title: Inhibition of neointimal hyperplasia with a novel zotarolimus coated balloon catheter
Authors: Bodo Cremers
John L. Toner
Lewis B. Schwartz
Randolf von Oepen
Ulrich Speck
Nicola Kaufels
Yvonne P. Clever
Dirk Mahnkopf
Michael Böhm
Bruno Scheller
Publication date: 01-06-2012
Publisher: Springer-Verlag
Published in: Clinical Research in Cardiology / Issue 6/2012
Print ISSN: 1861-0684
Electronic ISSN: 1861-0692
DOI: https://doi.org/10.1007/s00392-012-0415-7

Keynote webinar | Spotlight on medication adherence

Springer Medicine

Inhibition of neointimal hyperplasia with a novel zotarolimus coated balloon catheter

Abstract

Background

Methods

Results

Conclusion

Keynote webinar | Spotlight on medication adherence

Springer Medicine

Abstract

Background

Methods

Results

Conclusion

Please log in to get access to this content

Other articles of this Issue 6/2012

HMGB1 is an independent predictor of death and heart transplantation in heart failure

Glomus caroticum tumor as rare cause of recurrent syncope

Assessment of left atrial dysfunction in obstructive sleep apnea patients with the two dimensional speckle-tracking echocardiography

Frequency of heparin/platelet factor 4-dependent platelet antibodies in patients undergoing angioplasty and stenting for cardiovascular disease and their role for on-clopidogrel platelet reactivity

Impending paradoxical thromboembolism: thrombus caught in transit. A case report

Everolimus-eluting versus sirolimus-eluting stents: an updated meta-analysis of randomized trials