Transcript CAVATAS STUDY 5 years restenosis rate: 30% HR 0.43 (stent

Stenting:επαναστένωση
ISR (intra stent restenosis)
Μετεκπαιδευτικό Πρόγραμμα στην
Αγγειοχειρουργική - Ενδαγγειακή Χειρουργική
ΠΓΝΑ Αττικόν 09-02-2013
Κ. Α. Φίλης
Επίκ. Καθηγητής ΕΚΠΑ
Definitions
ISR can be defined clinically or angiographically.
Clinically, it is defined as the presentation of recurrent ischaemia
Angiographically, ISR is the presence of >50% diameter stenosis in
the stented segment.
50%-70% : moderate
Teirstein PS,
N Engl J Med, 1997
70%-99% : severe
Cellular response to injury
• Platelet adherence and degranulation (10-30min)
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Subenthothelial collagen exposure
Platelets adherence (αΙΙb βΙΙa, Von Villebrand, Fibronectin)
ADP, thromboxane A2,
Platelets recruitment (αΙΙb βΙΙIa)
Platelets degranulation (PDGF)
• Leukocyte, monocytes, macrophages
• SMC proliferation and migration (1day – 3months)
• Endothelial cell regrowth
Diffuse in stent restenosis
Initial role of stents : optional
to support the dissected ballooned plaque
from further dissection-rupture
to prevent arterial recoil by their radial
force
PTA result
PTA result
Intimal hyperplasia
Various ISR rates @ 1 year
according to locations
Time course of ISR
Factors influencing ISR
Cardiovascular risk factors
Endogenous risk factors
Exogenous factors
Cardiovascular factors
Smoking
Diabetes
Hyperlipidemia
Cardiovascular factors
Effect of smoking in ISR
Cardiovascular factors
Effect of diabetes in ISR
P=0.89 (NIDM)
P=0.04 (IDM)
Endogenous risk factors
Genomic
Blood flow
Plaque
Endogenous factors
Genomic
Endogenous factors
Blood flow
Endogenous factors
Plaque
Endogenous factors
Endogenous factors
Endogenous factors
Endogenous factors
Exogenous factors
Stent
Exogenous factors
Stent
Ευλυγισία
Πάχος
Ευκολία καθοδήγησης
Ακτινική δύναμη
Αρχιτεκτονική του πλέγματος
Βιοσυμβατότητα
Μηχανική αντοχή
Αντίσταση στη ρήξη
Exogenous factors
Stent asymetry
Exogenous factors
Self expanding V balloon expanded
Exogenous factors
Cell design
Exogenous factors
Strut Thickness
Exogenous factors
Stent fracture
Restenosis-Thrombosis
Pharmacologic prevention
ASA &
Heparin
ASA &
Ticlopidin
Restenosis-Thrombosis
Pharmacologic prevention
Gold standard : Clopidogrel + aspirin
Prevention of ISR
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Medicines
Drug eluting stents
Brachytherapy, Cryoplasty
Genes
Medicines
ISR on coronary PTA/stent
Reo pro
PDGF I
antiallergic
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, Pages 662-670
After 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.
Drug eluting stents
sirolimus
results from coronary
paclitaxel
DES inhibit smooth muscle cells and endothelial cells
1. They inhibit ISR
2. They are more thrombogenic
Clinical practice : no benefit in survival, no benefit in MACE,
But fewer reinterventions to keep the artery patent
DES in cardiac & peripheral arteries
Drug eluting stents in peripheral
arteries
J Endovasc Ther. 2009 Jun;16(3):251-60.
Infragenicular stent implantation for below-the-knee atherosclerotic disease:
clinical evidence from an international collaborative meta-analysis on 640 patients.
Biondi-Zoccai GG, Sangiorgi G, Lotrionte M, Feiring A, Commeau P, Fusaro M, Agostoni
P, Bosiers M, Peregrin J, Rosales O, Cotroneo AR, Rand T, Sheiban I.
Head-to-head comparisons showed that sirolimus-eluting stents
were superior to balloon-expandable bare metal stents in
preventing restenosis and increasing primary patency (both
p<0.001); sirolimus-eluting stents were also better than paclitaxeleluting stents in terms of primary patency (p<0.001) and repeat
revascularizations (p = 0.014).
Brachytherapy
Gene therapy
• Genetically engineered cells secreting a
thrombolytic enzyme (tPA) which are topically
applied (on the stent).
• Major problem : cells are moving away by the
blood flow.
Conclusions
ISR is a stable endothelial reaction to injury
STRATEGIES TO INHIBIT ISR
systematic
Medicines
topical
DES, Drug eluting balloons
Brachytherapy,
Cryoplasty
Photodynamic therapy
Genes