The Treatment of In-Stent Restenosis Neal Uren MD FRCP Consultant Cardiologist Royal Infirmary Edinburgh

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The Treatment of In-Stent RestenosisNeal Uren
MD FRCPConsultant CardiologistRoyal Infirmary
Edinburgh
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• MY CONFLICTS OF INTEREST ARE
• Travel, Accomodation Registration
• PCR - May 2006 (BosSci)
• TCT - October 2006 (BosSci)
• Travel Accomodation
• Guidant Institute visit, Brussels - February
  2006 (Abbott)
• Emerging Technologies Symposium -March 2006
  (BosSci)
• Annual SpR training, Malaga June 2006 (BosSci)

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The Real Problem of Clinical Restenosis
100
14
90
12
80
10
70
60
PCI for Restenosis
8
Stent Use
Stent
50
DES
6
40
30
4
20
2
10
0
0
'92
'93
'94
'95
'96
'97
'98
'99
'00
'01
'02
'03
'04
'05
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Predictors of In-Stent Restenosis

• Minimum IVUS stent area (MLA)
• Pre-intervention IVUS plaque burden
• Final MLD lt 3.0 mm
• Multiple stents
• Diabetes mellitus
• Chronic total occlusions
• Previous PTCA
• Proximal LAD stent
• Ostial location
• Long stents

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Cutting Balloon PCI for ISR
50
plt0.001 vs. rest
5.0
258 lesions
45
4.5
30-40 diffuse 50-60 focal
40
4.0
35
3.5
30
3.0
Percentage
mm
25
2.5


20
2.0

Stent
15
1.5
CBA
10
1.0
HSRA

5
0.5
PTCA
0
0
Acute
Late
Angio
TLR
Lumen
Lumen
restenosis
Gain
Loss
Loss index CBA 0.340.3, stent 0.640.4, rota
0.730.6
Adamian M et al, JACC 200138672
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Prediction of In-Stent Re-Restenosis

• Final MLD lt2.75 mm
• Diffuse in-stent restenosis
• Aggressive restenosis lt90 days
• POBA

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In-stent Restenosis An Unresolved Clinical
Problem
Mehran et al. Circulation 1999 100
1872-1878 Costantino et al. Am J Cardiol 2001
92 1214-1217
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Stairway to Evidence-Based Medicine
left maindisease
multi-vesseldisease
bifurcations
CTO
ISR
diabetes
TAXUS V ISR
long lesions
SISR
smallvessels
work-horse
Increasing complexity
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Taxus V Study Design
Patients with in-stent restenosis of a previously
implanted bare metal stent in a native coronary
artery lesion ?46mm in length and ?2.5 to
?3.75mm in diameter (n396)
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DES Strategy
Old stent
Area in which balloon was inflated against the
wall
Stented segment plus 5 mm on each edge
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Vascular Brachytherapy Approach
Old stent
Area in which balloon was inflated against the
wall
Area exposed to brachytherapy
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Cumulative TVR out to 9-MonthsSuperior Outcomes
for DES with Early Separation
25
17.4
20
15
Log-Rank P0.04
Cumulative Event Rate
10
5
10.4
0
0
30
60
90
120
150
180
210
240
270
300
Days Since Index Procedure
14
MLD Analysis Segment
9m Median (IQR) plt0.001
100 90 80 70 60 50 40 30 20 10 0
plt0.001
Pre-procedure
9m follow-up
Post-procedure
Percentile
0
1
2
3
4
Minimum Lumen Diameter (mm)
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9-Month Restenosis Superior with TAXUS DES
plt0.001
p0.81
p0.53
plt0.001
31.2
Patients
14.5
N/A
n
8/124
11/153
12/172
6/151
4/168
53/170
25/172
34/169
12/171
ProximalEdge
In-Stent
DistalEdge
AnalysisSegment
InjurySegment
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TAXUS V 9-Month Target Vessel Thrombosis
VBT
2.6(5/193)
1
3
1
p0.72
1.6(3/191)
DES
1
2
Target Vessel Thrombosis ()
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DES for ISR Study Design
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TAXUS V ISR In PerspectiveClinical 9-Month
Outcomes
0.270.65 mm
Late loss
0.290.54 mm
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TROPICAL Primary Endpoint 6-Month In-Lesion
Late Loss
Non-randomised trial, vessel size 2.5-3.0 mm,
lesion length lt45 mm
plt0.0001
1.5
Cypher DES, n 155
GAMMA I/II, n 221
1.0
mm
0.08
0.5
0.68
0
In-Lesion Late Loss
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SES vs. Historical Gamma VBT
TROPICAL
Clinical Outcome at 180 Days
Non
-
Hierarchical Event
Rate ()
TROPICAL
30
n 162 SES 262 VBT
plt0.001
GAMMA I/II
25
18.8
20
p0.490
p0.004
pPlt0.001
p0.080
15
14
10
9.4
5
3.7
3.9
2.5
2.0
1.8
0.6
0.6
0
Death
MI
Clinically
Stent
MACE
driven TLR
thrombosis
Neumann F-J Desmet W, PCR 2004
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E-Cypher Registry6 Months Follow-up MACE
4.0
3.8
3.0
3.0
Percentage
2.1
2.0
1.4
1.4
1.2
0.9
1.0
0.6
0.5
0.4
0.3
0.1
0.0
MACE
Death
STEMI
Non STEMI
TLR
TVR
non-ISR (n10,442)
ISR (n1,478)
CEC - adjudicated events all cases with death,
MI, TLR or reported stent thrombosis were reviewed
AHA 2004, New Orleans
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ISAR-DESIRE Trial
Kastrati et al, JAMA 2005293165
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ISAR-DESIRE Trial
Kastrati et al, JAMA 2005293165
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In-Stent Restenosis Conclusions

• The use of drug-eluting stents for the treatment
  of in-stent restenosis has been shown to be
• safe with low rates for target vessel
  thrombosis, myocardial infarction, late stent
  thrombosis
• effective TLR rate of 6.3-8.5 and an angio
  restenosis rate of 14.5-19.8 at 6-9 months
• when compared to vascular brachytherapy as the
  preexisting gold standard