2 ISR can be defined clinically or angiographically. DefinitionsISR can be defined clinically or angiographically.Clinically, it is defined as the presentation of recurrent ischaemiaAngiographically, ISR is the presence of >50% diameter stenosis inthe stented segment.50%-70% : moderate %-99% : severeTeirstein PS,N Engl J Med, 1997
3 Cellular response to injury Platelet adherence and degranulation (10-30min)Subenthothelial collagen exposurePlatelets adherence (αΙΙb βIΙa, Von Villebrand, Fibronectin)ADP, thromboxane A2,Platelets recruitment (αΙΙb βΙΙIa)Platelets degranulation (PDGF)Leukocyte, monocytes, macrophagesSMC proliferation and migration (1day – 3months)Endothelial cell regrowth
10 Το δίλημμα Αγγειοπλαστική με μπαλόνι Αγγειοπλαστική με ενδοπρόθεση Constrictive remodeling (αναδιαμόρφωση σύσπασης)Elastic recoil (ελαστική επαναφορά)Αγγειοπλαστική με ενδοπρόθεσηΑυξημένη μυο-ενδοθηλιακή υπερπλασία
40 Σημασία των αντιαιμοπεταλιακών Αναστολή αιμοπεταλιακής δραστικότηταςμε σκοπό την πρόληψη της οξείαςθρόμβωσης της αγγειοπλαστικήςΑνεπαρκή για την επαναστένωση
41 Prevention of ISR Medicines Drug eluting stents Brachytherapy, CryoplastyGenes
42 Medicines ISR on coronary PTA/stent Reo proPDGF Iantiallergic
43 Induction of vascular atrophy as a novel approach to treating restenosis. A review Seung-Kee Min MDa, Richard D. Kenagy PhDb and Alexander W. Clowes MDb, ,Journal of Vascular Surgery Volume 47, Issue 3, March 2008, PagesAfter vascular reconstruction, luminal narrowing is in part caused by intimal thickening, the consequence of endothelial injury and inflammation, smooth muscle cell hyperplasia, and extracellular matrix accumulation. It may be possible to induce these lesions to shrink. This novel approach to the treatment of restenosis is supported by animal experiments and a few clinical observations demonstrating vascular atrophy in response to drugs such as Gleevec (EDGF I). A potential limitation to this approach might be the formation of aneurysms.
44 But fewer reinterventions to keep the artery patent Drug eluting stentssirolimus (rapamycin) paclitaxelinhibit smooth muscle cells and endothelial cellsThey inhibit ISRThey are more thrombogenicClinical practice : no benefit in survival, no benefit in MACE,But fewer reinterventions to keep the artery patent
45 Drug eluting stents in peripheral arteries SMART (SIROLIMUS) CORDIS ENDOVASCULARZILVER (PACLITAXEL) COOK
46 Drug eluting balloons in peripheral arteries THUNDER trial (Local Taxane with ShortExposure for Reduction of Restenosis in Distal Arteries), 2008Femoral Paclitaxel (FemPac) trial, 2008ILLUMENATE trial, 2013, euroPCRDANCE trial, 2013, MEET (subenthothelial dexamethazone injections)
52 Gene therapyGenetically engineered cells secreting a thrombolytic enzyme (tPA) which are topically applied (on the stent).Major problem : cells are moving away by the blood flow.
53 STRATEGIES TO INHIBIT ISR ConclusionsISR is a stable endothelial reaction to injurySTRATEGIES TO INHIBIT ISRsystematic topicalMedicines DES, Drug eluting balloonsBrachytherapy,CryoplastyPhotodynamic therapyGenes
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