Coronary stenting is commonly used to treat coronary disease but often leads to restenosis of the artery. Restenosis involves thrombosis, inflammation, and smooth muscle cell growth forming scar tissue. It is clinically defined as recurrent ischemia and angiographically as over 50% diameter stenosis. Drug-eluting stents significantly reduce restenosis by inhibiting cell proliferation through local drug release but increase thrombosis risk requiring prolonged anticoagulation. Restenosis results from overlapping biological processes after stenting and achieving its perfect elimination remains a challenge.

1. Coronary Restenosis After Stent
Implantation
Presented by Michael Mullokandov
Supervised by David Gutterman, MD

2. Coronary stenting and restenosis
• Percutaneous coronary intervention with stenting is the most
widely performed procedure for the treatment of
symptomatic coronary disease.
• A major complication after re-vascularisation procedures
is restenosis of the injured artery.
• Several stages involved in this process include thrombus
formation, inflammatory cell infiltration and smooth muscle
cell (SMC) accumulation to form neointimal lesions.

3. Restenosis leading cascade
Restenosis can be defined clinically or angiographically.
• Clinically, it is defined as the presentation of recurrent ischemia.
• Angiographically, restenosis is the presence of >50% diameter stenosis in
the stented segment.
• Restenosis can occur either early (immediately following the procedure or
up to a few weeks after the procedure) or late (weeks or months after the
intervention).

4. Intracoronary stenting
 There are two main types of stents currently in use :
American Heart Association. Drug-eluting stents beat bare metal stents in diabetics
Drug-Eluting
(DES)
• Coated with a drug that
fights the proliferation
of cells
• Significantly reduce the
need of repeated
procedures
• Prolonged need in
anticoagulatory therapy
Bare-Metal
(BMS)
• Made of stainless steel
• Procedure involves
lower costs than with
DES
• Higher risk of restenosis
Nine of 39 patients with
DES (23.1%)
Int J Angiol. 2010 Summer; 19(2): e66–e72
20 of 41 patients with
BMS (48.8%)
Developed restenosis

5. Endothelial response due to stenting
• The primary effect of stenting could be seen on endothelial cells which are
hardly damaged during the procedure.
• The response of the endothelium to stenting can be divided into three
phases: endothelial denudation, re-endothelialization, and/or
neoendothelium.
Endothelialization was more complete in bare-metal stents than in drug-
eluting stents at both 3 days (P=.016) and 7 days (P=.0001)
Rev Esp Cardiol. 2011;64:159-62. - Vol. 64 Num.02 DOI: 10.1016/j.rec.2010.04.001

6. Inflammatory response due to stenting
• Endothelium injury and foreign body stent placement lead to the
response of the activation of platelets and their deposition at the site of
the lesion, with recruitment of circulating leucocytes.
• A multistep cascade of platelet and leukocyte adhesion molecules direct
leukocyte adhesion to the adherent platelets in a process termed
“secondary capture.”
Local inflammation stimulates vascular
smooth muscle cell (SMC) proliferation and
extracellular matrix deposition, resulting in
neointimal thickening and restenosis.

7. Tissue remodeling
• The modification of SMCs is
activated by growth
factors/cytokines produced by the
injured endothelium and media,
platelets, and infiltrated
inflammatory cells.

8. Restenosis processes and inhibitors

9. Restenosis treatment and prevention
• Radiation—intravascular brachytherapy.
Intracoronary brachytherapy, using either β or γ sources reduces neointimal
accumulation, probably by blocking cell proliferation, inducing apoptosis, and
inhibiting cell migration.
Unfortunately brachytherapy also has
significant harmful dose related effects:
• Late thrombosis
• Paradoxical stenosis at the ends or
outside of the stents
• Acceleration of neointimal thickening
• Failure of endothelial regeneration

10. • Drug eluting stents
The invention of the drug-eluting stent came into the angiographic procedures in 2002.
The three major elements of drug-eluting stents are:
• Stent
• Drug
• The mechanism for controlling drug release (usually a polymer to protect and control
release)
Although drug-eluting stents continue to represent a major medical advance
for angioplasty, new clot thrombosis formation with stents represent a problem.
Clotting suppressant agents are routinely given during placement, and anticlotting
agents should be continued; the question is for how long…
Restenosis treatment and prevention

11. The bottom line
• Restenosis is caused by a number of overlapping
biological processes, with different time courses.
• Despite the addition of DES to the arsenal of
coronary intervention procedures, the ‘perfect’
solution to eliminate restenosis after coronary
intervention is still not available.