Stenting:epa?ast???s? ISR (intra stent restenosis)

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Stentingepa?ast???s?ISR (intra stent restenosis)
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• Definitions
• ISR can be defined clinically or
  angiographically.
• Clinically, it is defined as the presentation of
  recurrent ischaemia
• Angiographically, ISR is the presence of gt50
  diameter stenosis in
• the stented segment.
• 
  50-70 moderate 70-99
  severe

Teirstein PS, N Engl J Med, 1997
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Cellular response to injury

• Platelet adherence and degranulation (10-30min)
• Subenthothelial collagen exposure
• Platelets adherence (a??b ß??a, Von Villebrand,
  Fibronectin)
• ADP, thromboxane A2,
• Platelets recruitment (a??b ß??Ia)
• Platelets degranulation (PDGF)
• Leukocyte, monocytes, macrophages
• SMC proliferation and migration (1day 3months)
• Endothelial cell regrowth

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Diffuse in stent restenosis
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Initial role of stents optional

• to support the dissected ballooned plaque
• from further dissection-rupture
• to prevent arterial recoil by their radial
• force

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PTA result
PTA result
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Intimal hyperplasia
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Various ISR rates _at_ 1 year according to locations
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Time course of ISR
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Factors influencing ISR
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Cardiovascular factors
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Effect of smoking in ISR
Cardiovascular factors
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Effect of diabetes in ISR
Cardiovascular factors
P0.89 (NIDM) P0.04 (IDM)
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Endogenous risk factors
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Genomic
Endogenous factors
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Blood flow
Endogenous factors
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Plaque
Endogenous factors
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Endogenous factors
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Endogenous factors
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Endogenous factors
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Endogenous factors
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Exogenous factors
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Stent
Exogenous factors
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Stent asymetry
Exogenous factors
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Self expanding V balloon expanded
Exogenous factors
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Cell design
Exogenous factors
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Strut Thickness
Exogenous factors
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Stent fracture
Exogenous factors
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Restenosis-ThrombosisPharmacologic prevention
ASA Heparin
ASA Ticlopidin
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Restenosis-ThrombosisPharmacologic prevention
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Gold standard Clopidogrel aspirin
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Prevention of ISR

• Medicines
• Drug eluting stents
• Brachytherapy, Cryoplasty
• Genes

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Medicines ISR on coronary PTA/stent
Reo pro
PDGF I
antiallergic
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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 SurgeryVolume 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.

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Drug eluting stents

• sirolimus
• results from
  coronary
• paclitaxel
• DES inhibit smooth muscle cells and endothelial
  cells
• They inhibit ISR
• They are more thrombogenic
• Clinical practice no benefit in survival, no
  benefit in MACE,
• But fewer reinterventions to keep the artery
  patent

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DES in cardiac peripheral arteries
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Drug eluting stents in peripheral arteries

• J Endovasc Ther. 2009 Jun16(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 plt0.001) sirolimus-eluting stents
were also better than paclitaxel-eluting stents
in terms of primary patency (plt0.001) and repeat
revascularizations (p 0.014).
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Brachytherapy
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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.

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Conclusions

• ISR is a stable endothelial reaction to injury
• STRATEGIES TO INHIBIT ISR
• systematic topical
• Medicines
  DES, Drug eluting balloons
• Brachytherapy,
• Cryoplasty
• 
  Photodynamic therapy
• Genes