In-Stent Restenosis

DR. SUBHASH DUKIYA

25.2.2016

In-Stent Restenosis: Definitions

• “Angiographic” Restenosis

• Late lumen loss with > 50% diameter stenosis at

the stent segment or its edges (5-mm segments

adjacent to the stent)in follow-up

• “Clinical” Restenosis

– Symptom or ischemia recurrence with >50%

diameter stenosis,

– Or >70% diameter stenosis without symptoms

Modified from Dangas et al. JACC 2010; 56:1897-1907

• Incidence

• BMS- 20-30%

• DES- upto 12%

Cutlip, D. E. et al. J Am Coll Cardiol 2002;40:2082-2089

Clinical restenosis rates: target lesion revascularization (TLR), target vessel

revascularization (TVR), or target vessel failure (TVF):

at 6, 9, or 12 months

n/a

Endeavor II(n=581/598)

Sirius(n=501/525)

Taxus IV(n=618/650)

Late TLR “Creep” seen with All DES in long term followup

5.96.5

7.2 7.2

R2 = 0.9524

0

2

4

6

8

10

1 2 3 4 5

Years of Follow-up

4.9

6.8

7.9

9.4

6.3

R2 = 0.9762

0

2

4

6

8

10

1 2 3 4 5

Years of Follow-up

TL

R (

%)

4.4

5.6

6.9

7.8

9.1

R2 = 0.9973

0

2

4

6

8

10

Years of Follow-up

TL

R (

%)

1 2 3 4 5

4 Year Clinical Results of TAXUS IV, Stone, ACC 20064 year Outcomes in the Sirius Trial, Leon, TCT 2006

Endeavor II 4 year : Fajadet et al. PCR 2008Modified from Popma, J

Stent Restenosis

• Pathophysiology of restenosis is different

– Balloon angioplasty restenosis:

• occurs primarily because of elastic recoil and

negative remodeling of the vessel

– Stent restenosis:

• occurs primarily because of neointimal hyperplasia

Cutlip et al. JACC 2002; 40:2082-9

Stent Restenosis

• Different mechanism

than after balloon

angioplasty

• Stent restenosis is

secondary to tissue

ingrowth (neointimal

hyperplasia) within the

stent

Copyright ©2010 American College of Cardiology Foundation. Restrictions may apply.

Pathway Leading to In-Stent Restenosis After Stent

Implantation

Garg, S. et al. J Am Coll Cardiol 2010;56:S1-S42

Patterns of In-Stent Restenosis

Articulation or Gap

Margin

Focal Body

Multifocal

Focal

Intra-stent Proliferative

Total Occlusion

Diffuse

Adapted from Mehran R et al. Circulation 1999;100:1872-78Courtesy of Popma, J

Date of download: 2/16/2016 Copyright © The American College of Cardiology. All rights reserved.

From: Current Treatment of In-Stent Restenosis

J Am Coll Cardiol. 2014;63(24):2659-2673. doi:10.1016/j.jacc.2014.02.545

Pathological Images of In-Stent Restenosis

Low-power (A and B, 4×) and high-power (C and D, 10×) magnification images of restenosis within (A and C) a bare-metal stent

(BMS) and (B and D) a drug-eluting stent (DES), both implanted 5 years antemortem. In the BMS, the dominant pathology is smooth

muscle cell-rich neointimal hyperplasia. There is also some chronic inflammation with neovascularization around stent struts (green

arrowhead). In the DES, there is presence of neoatherosclerosis with formation of a necrotic core (black arrowheads) and

calcification (grey arrowheads).

Figure Legend:

Date of download: 2/16/2016 Copyright © The American College of Cardiology. All rights reserved.

From: Current Treatment of In-Stent Restenosis

J Am Coll Cardiol. 2014;63(24):2659-2673. doi:10.1016/j.jacc.2014.02.545

Patterns of In-Stent Restenosis as Depicted by Optical Coherence Tomography

(A) Homogeneous bright neointimal proliferation. (B) Uniform neointimal proliferation with microvessels (arrows). (C) Layered

pattern with multiple microvessels (arrows) in the dark layer overlying the stent struts. (D) Multilayered pattern. *Wire artifact.

Figure Legend:

Predictors of clinical restenosis• Type of underlying stent

• Underlying substrate( Underexpansion, geographic miss)

• Stent fractures

• Final Minimum Lumen Diameter (MLD)

• Reference Diameter

• Stent length

• Lesion length

• Diabetes

• drug resistance or local hypersensitivity reactions,for

DES failure

From Cutlip et al; JACC 2002; 40:2082-9

Stent Underexpansion

from Dangas et al. JACC 2010; 56:1897-1907

• Presentation-• ISR is a relatively benign clinical entity, with predominantly stable

clinical presentation and largely satisfactory acute results with

repeat interventions . This was in keeping with the prevailing

etiologic paradigm suggesting that the progressive homogeneous

smooth muscle cell proliferation constituted the universal substrate

of ISR.

• recent studies, however, suggest that patients with ISR frequently

present with unstable symptoms and, in fact, many of them exhibit

elevations of cardiac markers fulfilling diagnostic criteria for

myocardial infarction .

• Whether acute coronary syndrome presentations are more common

with DES-ISR remains unknown.

Date of download: 2/16/2016 Copyright © The American College of Cardiology. All rights reserved.

From: Current Treatment of In-Stent Restenosis

J Am Coll Cardiol. 2014;63(24):2659-2673. doi:10.1016/j.jacc.2014.02.545

OCT Images of a Patient Who Presented With Prolonged Chest Pain 3 Years After the Implantation of an Everolimus-Eluting Stent in

the Left Anterior Descending Coronary Artery

Angiography demonstrated in-stent restenosis (ISR), but the patient developed a significant enzymatic rise, diagnostic of a

myocardial infarction. (A) Homogeneous neointimal hyperplasia. (B) Bright neointima completely shadowing the stent struts

(consistent with lipid-laden or infiltrated neointima). (C and D) Images of a ruptured thin cap (arrows) with underlying cavities (+),

together with large protruding red thrombi (T) causing major distal shadowing of the stent. *Wire artifact. OCT = optical coherence

tomography.

Figure Legend:

Date of download: 2/16/2016 Copyright © The American College of Cardiology. All rights reserved.

From: Current Treatment of In-Stent Restenosis

J Am Coll Cardiol. 2014;63(24):2659-2673. doi:10.1016/j.jacc.2014.02.545

OCT Findings in a Patient Presenting With a Non–ST-Segment Elevation Myocardial Infarction 8 Years After Treatment of a Lesion in

the Left Circumflex Coronary Artery With a BMS

(A) Angiography disclosed focal in-stent restenosis with large thrombus (white arrow) within the stent (arrowheads). (B) OCT

disclosed mild homogeneous neointimal hyperplasia at the distal stent segment. (C) Proximally, a large, protruding red thrombus

(T) was confirmed. The proximal segments of the stent (D and E) showed findings consistent with neoatherosclerosis: glistening

neointima with attenuation (+), with a ruptured thin-cap fibroatheroma (yellow arrow). *Wire artifact. Abbreviations as in Figures 1

and 3.

Figure Legend:

Treatment of In-Stent Restenosis

• IVUS, OCT role

• balloon angioplasty

• Brachytherapy

• BMS

• DCB

• DES

Date of download: 2/16/2016 Copyright © The American College of Cardiology. All rights reserved.

From: Current Treatment of In-Stent Restenosis

J Am Coll Cardiol. 2014;63(24):2659-2673. doi:10.1016/j.jacc.2014.02.545

Diameter Stenosis at Follow-up in the RIBS II Study

BA = balloon angioplasty; FU = follow-up (broken lines); RE = binary restenosis rate; RIBS II = Restenosis Intrastent: Balloon

Angioplasty Versus Elective Sirolimus-Eluting Stenting; SES = sirolimus-eluting stent(s).

Figure Legend:

Date of download: 2/16/2016 Copyright © The American College of Cardiology. All rights reserved.

From: Current Treatment of In-Stent Restenosis

J Am Coll Cardiol. 2014;63(24):2659-2673. doi:10.1016/j.jacc.2014.02.545

Comparative Efficacy of DCB, DES, and BA in the Treatment of Restenosis Within DES

Cumulative frequency distribution curves for percent diameter stenosis at 6- to 8-month angiographic surveillance in the ISAR-

DESIRE 3 (Intracoronary Stenting and Angiographic Results: Drug Eluting Stents for In-Stent Restenosis) randomized trial. DCB =

drug-coated balloon; other abbreviations as in Figures 1 and 5.

Figure Legend:

• Overall, DCB were associated with a higher risk of repeat

revascularisation than with EES and a similar risk to other DES.

• EES was the top-ranked treatment in all assessed subgroups.

• In the DES ISR subgroup, EES was the top-ranked treatment,

PES the second, and SES the third, whereas EES and PES were

associated with signifi cantly lower risk of repeat

revascularisation than with DCB (EES OR 0·38 [95% CI 0·16–

0·88]; PES 0·61 [0·38–0·98]).

DES for treatment of DES restenosis

• Only one randomized trial: ISAR-DESIRE 2

– Sirolimus (SES) or Paclitaxel (PES) stents for

Sirolimus in-stent restenosis

– Angiographic restenosis 20%

– TLR about 16%

– No difference between SES or PES

Mehilli, J. et al. J Am Coll Cardiol 2010;55:2710-2716

Mehilli, J. et al. J Am Coll Cardiol 2010;55:2710-2716

ISAR DESIRE-2: DES for DES In-Stent Restenosis:

Angiographic Restenosis at 6 to 8 Months and Clinical

Restenosis at 1 Year

Dangas, G. D. et al. J Am Coll Cardiol 2010;56:1897-1907

Algorithm for the Treatment of DES Restenosis

Patterns of DES restenosis affect subsequent

outcome

• Study of 250 restenotic DES lesions

– Divided into focal (65%) and nonfocal (35%)

– Treated with repeat DES (57% of focal, 69% of nonfocal), or POBA

– Recurrent restenosis occurred in only 18% of focal lesions vs 51% of nonfocal lesions

– TLR higher in the nonfocal group as well (10% vs 23%)

– Diabetes also a strong predictor of recurrent restenosis

Cosgrave et al. J Am Coll Cardiol 2006;47:2399–404

Summary

• Treatment of in-stent restenosis:

1.DES and DCB.

2. DES ISR – EES and PES better than DEB.

THANK YOU