Advertisement

Local catheter-based delivery of antithrombotic or antiproliferative drugs: A new concept for prevention of restenosis

      Abstract

      Background

      Drug eluting stents have reduced the incidence of restenosis after percutaneous coronary interventions significantly, but cause concern about long term safety. Local drug delivery using special application catheters is an alternative approach for intracoronary pharmacotherapy. Besides the fact, that no problematic coating as drug carrier has to be used, a local delivery independent of the stent itself by using catheter techniques offers further advantages – such as the possibility to treat the whole vessel wall, stent edges and adjacent vessel segments and not only the area close to the stent struts.

      Methods and Results

      We have developed a new local catheter-based delivery system for local intracoronary pharmacotherapy. An antithrombotic as well as an antiproliferative therapy concept for prevention of restenosis are presented in the manuscript. Our data show that local drug delivery of platelet glycoprotein VI and paclitaxel were effective in the reduction of thrombus formation and neointima formation in experimental animal models.

      Conclusions

      A combination of early antithrombotic and antiatherosclerotic mechanisms may be a realistic and effective approach to minimize postinterventional thromboischemic events and neointima formation. These results may contribute to an advanced and even combined local intracoronary pharmacotherapy in near future, independent of stent coatings.

      Keywords

      To read this article in full you will need to make a payment

      Purchase one-time access:

      Academic & Personal: 24 hour online accessCorporate R&D Professionals: 24 hour online access
      One-time access price info
      • For academic or personal research use, select 'Academic and Personal'
      • For corporate R&D use, select 'Corporate R&D Professionals'

      Subscribe:

      Subscribe to Thrombosis Research
      Already a print subscriber? Claim online access
      Already an online subscriber? Sign in
      Institutional Access: Sign in to ScienceDirect

      References

        • Teirstein P.S.
        Living the dream of no restenosis.
        Circulation. 2001; 104: 1996-1998
        • Lincoff A.M.
        • Topol E.J.
        Interventional catheterization techniques.
        in: Braunwald E. Heart disease. A textbook of cardiovascular medicine. Fifth edition. W. B. Saunders, Philadelphia1997: 1366-1391
        • Silber S.
        Antiproliferative coated stents and intracoronary brachytherapy: common traits and differences.
        Z Kardiol. 2002; 91: 443-457
        • Eisenberg M.J.
        • Konnyu K.J.
        Review of randomized clinical trials of drug-eluting stents for the prevention of in-stent restenosis.
        Am J Cardiol. 2006; 98: 375-382
        • Tung R.
        • Kaul S.
        • Diamond G.A.
        • Shah P.K.
        Narrative review: drug-eluting stents for the management of restenosis: a critical appraisal of the evidence.
        Ann Intern Med. 2006; 144: 913-919
        • Kotani J.
        • Awata M.
        • Nanto S.
        • Uematsu M.
        • Oshima F.
        • Minamiguchi H.
        • et al.
        Incomplete neointimal coverage of sirolimus-eluting stents: angioscopic findings.
        J Am Coll Cardiol. 2006; 47: 2108-2111
        • Nebeker J.R.
        • Virmani R.
        • Bennett C.L.
        • Hoffman J.M.
        • Samore M.H.
        • Alvarez J.
        • et al.
        Hypersensitivity cases associated with drug-eluting coronary stents: a review of available cases from the Research on Adverse Drug Events and Reports (RADAR) project.
        J Am Coll Cardiol. 2006; 47: 175-181
        • Joner M.
        • Finn A.V.
        • Farb A.
        • Mont E.K.
        • Kolodgie F.D.
        • Ladich E.
        • et al.
        Pathology of drug-eluting stents in humans: delayed healing and late thrombotic risk.
        J Am Coll Cardiol. 2006; 48: 193-202
        • Feres F.
        • Costa Jr., J.R.
        • Abizaid A.
        Very late thrombosis after drug-eluting stents.
        Catheter Cardiovasc Interv. 2006; 68: 83-88
        • Massberg S.
        • Gawaz M.
        • Gruner S.
        • Schulte V.
        • Konrad I.
        • Zohlnhoefer D.
        • et al.
        A crucial role of glycoprotein VI for platelet recruitment to the injured arterial wall in vivo.
        J Exp Med. 2003; 197: 41-49
        • Nieswandt B.
        • Watson S.P.
        Platelet-collagen interaction: is GPVI the central receptor?.
        Blood. 2003; 102: 449-461
        • Massberg S.
        • Konrad I.
        • Bultmann A.
        • Schulz S.
        • Muench G.
        • Peluso M.
        • et al.
        Soluble glycoprotein VI dimer inhibits platelet adhesion and aggregation to the injured vessel wall in vivo.
        FASEB J. 2004; 18: 397-399
        • Gawaz M.
        • Konrad I.
        • Hauser A.I.
        • Sauer S.
        • Li Z.
        • Wester H.J.
        • et al.
        Non-invasive imaging of glycoprotein VI binding to injured arterial lesions.
        Thromb Haemost. 2005; 93: 910-913
        • Lincoff A.M.
        • Topol E.J.
        • Ellis S.G.
        Local drug delivery for the prevention of restenosis. Fact, fancy and future.
        Circulation. 1994; 90: 2070-2084
        • Popma J.J.
        • Califf R.M.
        • Topol E.J.
        Clinical trials of restenosis after coronary angioplasty.
        Circulation. 1991; 84: 1426-1436
        • Wilensky R.L.
        • March K.L.
        • Gradus-Pizlo I.
        • Spaedy A.J.
        • Hathaway D.R.
        Methods and devices for local drug delivery in coronary and peripheral arteries.
        Trends Cardiovasc Med. 1993; 3: 163-170
        • Herdeg C.
        • Oberhoff M.
        • Baumbach A.
        • Blattner A.
        • Axel D.I.
        • Schröder S.
        • et al.
        Local paclitaxel delivery for the prevention of restenosis: biological effects and efficacy in vivo.
        J Am Coll Cardiol. 2000; 35: 1969-1976
        • Herdeg C.
        • Oberhoff M.
        • Baumbach A.
        • Schroeder S.
        • Leitritz M.
        • Blattner A.
        • et al.
        Effects of local all-trans-retinoic acid delivery on experimental atherosclerosis in the rabbit carotid artery.
        Cardiovasc Res. 2003; 57: 544-553
        • Wolinsky H.
        • Thung S.N.
        Use of a perforated balloon catheter to deliver concentrated heparin into the wall of the normal canine artery.
        J Am Coll Cardiol. 1990; 15: 475-481
        • Lambert C.L.
        • Leone J.E.
        • Rowland S.M.
        Local drug delivery catheters: functional comparison of porous and microporous designs.
        Coron Artery Dis. 1993; 4: 469-475
        • Herdeg C.
        • Oberhoff M.
        • Baumbach A.
        • Blattner A.
        • Küttner A.
        • Schröder S.
        • et al.
        Visualization and comparison of drug effects after local paclitaxel delivery with different catheter types.
        Basic Res Cardiol. 1999; 94: 454-463
        • Ruggeri Z.M.
        Platelets in atherothrombosis.
        Nat Med. 2002; 8: 1227-1234
        • Bultmann A.
        • Herdeg C.
        • Li Z.
        • Münch G.
        • Baumgartner C.
        • Langer H.
        • et al.
        Local delivery of soluble platelet collagen receptor glycoprotein VI inhibits thrombus formation in vivo.
        Thromb Haemost. 2006; 95: 763-766
        • Schiff P.B.
        • Fant J.
        • Horwitz S.B.
        Promotion of microtubule assembly in vitro by taxol.
        Nature. 1979; 277: 665-667
        • Rowinsky E.K.
        • Donehower R.C.
        Paclitaxel (Taxol). Review article.
        N Engl J Med. 1995; 332: 1004-1014
        • Jordan M.A.
        • Toso R.J.
        • Thrower D.
        • Wilson L.
        Mechanism of mitotic block and inhibition of cell proliferation by taxol at low concentrations.
        Proc Natl Acad Sci USA. 1993; 90: 9552-9556
        • Axel D.I.
        • Kunert W.
        • Göggelmann C.
        • Oberhoff M.
        • Herdeg C.
        • Küttner A.
        • 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
        • Herdeg C.
        • Oberhoff M.
        • Siegel-Axel D.I.
        • Baumbach A.
        • Blattner A.
        • Küttner A.
        • et al.
        Paclitaxel: Ein Chemotherapeutikum zur Restenoseprophylaxe? Experimentelle Untersuchungen in vitro und in vivo.
        Z Kardiol. 2000; 89: 390-397
        • Dommke C.
        • Haase K.K.
        • Süselbeck T.
        • Streitner I.
        • Haghi D.
        • Metz J.
        • Borggrefe M.
        • Herdeg C.
        Local paclitaxel delivery after coronary stenting in an experimental animal model.
        Thromb Haemost. 2007; 98: 674-680
        • Stone G.W.
        • Ellis S.G.
        • Cox D.A.
        • et al.
        A polymer- based, paclitaxel- eluting stent in patients with coronary artery disease.
        N Engl J Med. 2004; 350: 221-231
        • Shuchman M.
        Debating the risks of drug-eluting stents.
        N Engl J Med. 2007; 356: 325-328
        • Tanabe K.
        • Serruys P.W.
        • Degertekin M.
        • Guagliumi G.
        • Grube E.
        • Chan C.
        • et al.
        Chronic arterial responses to polymer-controlled paclitaxel-eluting stents: comparison with bare metal stents by serial intravascular ultrasound analyses: data from the randomized TAXUS-II trial.
        Circulation. 2004; 109: 196-200
        • Silber S.
        Cypher versus taxus: are there differences?.
        J Interv Cardiol. 2005; 18: 441-446