in-stent restenosis - nvhvv carvasz 2014/s24_1_k_boerlage_van_dijk.pdfballoon in in-stent restenosis...
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IN-STENT RESTENOSIS
K.Boerlage-van Dijk
CarVasZ 2014
Definition ISR
• Angiographic: recurrent diameter stenosis >50%
at the stent segment or edges (5-mm segments
adjacent to stent)
• Mehran system morphological classification BMS-
ISR (need for repeat revascularization)
I Focal (19%)
II Diffuse (35%)
III Proliferative (50%)
IV Occlusion (98%)
Mehran R. et al. Circulation 1999
Underlying substrate
• Underexpansion
• Stent misplacement or stents not fully covering
underlying lesion
• Stent fractures
• In DES: drug resistance or local hypersensitivity
reactions
Pathological images
Courtesy of Dr.
M. Joner,
CVPath Inc.
Gaithersburg,
Maryland
Pathology neoatherosclerosis BMS vs
DES• Incidence greater in DES (31%) than BMS (16%)
• Median stent duration shorter in DES (420 days) than in BMS (2160 days)
• Unstable lesions (thin-cap fibroatheromas or plaque rupture) more frequent in BMS (7.4%) than DES (3.1%)
Nakazawa G. et al. JACC 2011
Clinical presentation
• Asymptomatic
• Stable clinical presentation
• Unstable symptoms
• Elevation of cardiac markers
Incidence and treatment ISR
• High incidence of in-stent restenosis after PCI
with BMS
• Reduction incidence ISR after PCI with DES, but
restenosis still occurs
• Treatment by angioplasty with conventional
balloons, BMS, cutting balloons, rotablation and
brachtherapy unsatisfactory results
• ISR commonly treated by DES
Disadvantages DES
• Delayed healing
• Chronic inflammatory reaction (polymeric matrix)
• Late and very late stent thrombosis
• Inhomogeneous drug delivery
• In ISR double layer of stents
Drug Eluting Balloon
• 3ug/mm2 paclitaxel
• Uniform and complete release target drug dose after first balloon expansion
• Used for ISR, small vessel disease and side branches in bifurcations
Drug eluting balloon
• Delivering biologically active drug
• No permanent foreign body
• Uniform drug release
• No inflammation from polymer
• Prevention of thrombosis
• Reduced time period for anti-platelet therapy
Hwang, Circulation 2001; 104: 600-5
DES
SeQuent Please
Equal Drug Distribution with DEB
PI: Bruno Scheller
PACCOCATH ISR I and II
A Prospective, Randomized Trial of a Paclitaxel-Eluting
Balloon in In-Stent Restenosis
Klinik für Innere Medizin III, Universitätsklinikum des Saarlandes,
Homburg / Saar, Germany
PI: Bruno Scheller
PACCOCATH ISR I and II
A Prospective, Randomized Trial of a Paclitaxel-Eluting
Balloon in In-Stent Restenosis
Klinik für Innere Medizin III, Universitätsklinikum des Saarlandes,
Homburg / Saar, Germany
Results QCA / primary endpoint: In-segment analysis at 6
months
Control DEB p
Lesion length 18.2 ± 7.9 mm 17.9 ± 6.1 mm 0.868
Reference diameter 3.03 ± 0.37 mm 2.93 ± 0.47 mm 0.463
Minimal lumen diameter initial 0.69 ± 0.39 mm 0.72 ± 0.35 mm 0.811
Minimal lumen diameter post PTCA 2.52 ± 0.47 mm 2.44 ± 0.55 mm 0.603
Minimal lumen diameter 6 months 1.71 ± 0.91 mm 2.30 ± 0.74 mm 0.020
Late lumen loss (in segment) 0.82 ± 0.86 mm 0.13 ± 0.51 mm 0.002
Binary restenosis rate 40.9 % 8.7 % 0.017
PACCOCATH ISR I/II
Late lumen loss - ISR I vs. ISR II
0.0
0.2
0.4
0.6
0.8
1.0
1.2
1.4
1.6
1.8
late loss in-stent
ISR I
late loss in-
segment ISR I
late loss in-stent
ISR II
late loss in-
segment ISR II
[mm
]
Uncoated balloon Drug-coated balloon
p < 0.01p < 0.01
p < 0.01 p < 0.01
November 1, 2006
PEPCAD II Trial
“The Paclitaxel-Eluting PTCA-Balloon Catheter in
Coronary Artery Disease to Treat In-Stent Restenoses:
A Comparison to the Paclitaxel-Eluting Taxus™ Stent - A Pilot Study”
PI: Martin Unverdorben
Results: 6 Months FU (As
Treated)
PEPCAD II SeQuent
Please
N=66
Taxus
N=60
p-value
Follow-up [mo] 6.2±0.8 6.2±0.8 0.70
Follow-up: clinical 62 (93.9%) 59 (98.3%) 0.40
Late loss [mm] 0.19±0.39 0.45±0.69 0.01
Restenosis
(segment)
2/54 (3.7%) 11/53 (20.8%) 0.02
TLR 2/62 (3.2%) 11/59 (18.6%) >0.01
Myocardial
infarction
0/62 (0.0%) 1/59 (1.7%) 1.00
Death 1/62 (1.6%) 1/59 (1.6%) 1.00
Total MACE 3/62 (4.8%) 13/59 (22.0%) >0.01
19
PEPCAD II
No. at risk
Drug-coated balloon 70 70 67 65 64 63 62
Drug-eluting stent 60 58 56 53 47 47 46
B
No. at risk
Drug-coated balloon 70 70 67 65 64 63 62
Drug-eluting stent 60 58 56 53 47 47 46
B
Freedom from stent thrombosis, target lesion revascularization, myocardial infarction,
and death
ISAR-DESIRE 3ISAR-DESIRE 3
DEB, PES, BA in patients with restenosis after implantation of a DES: a randomised, open label trial
Byrne R.A. et al. Lancet 2013; 461-67
Primary EndpointDiameter Stenosis at Follow-up Angiography
Secondary Endpoint
Binary Restenosis Target Lesion Revascularization
ISAR-DESIRE 3RIBS V
A randomized comparison of DEB vs EES in
patients with BMS ISR
Alfonso F. et al. JACC 2014; 1378-86
ISAR-DESIRE 3The SEDUCE
OCT study of healing characteristics of DEB vs EES for ISR randomised clinical trial
Adriaenssens T. et al. EuroIntervention 2014; 439-448
Conclusion
• DEB leaves fewer stent struts uncovered at 9
month FU
• EES lower percentage of diameter stenosis at 9
month FU
• DEB slightly better safety profile
• This did not translate into differences in clinical
outcome.
• The use of both DEB and EES valuable treatment
options for ISR.
DARE trial
• Multicenter, randomized study
• 270 Patients with ISR in BMS or DES
• SeQuent Please VS Xience Prime
• Primary Endpoint: Minimal lumen diameter at 6
months
OLVG
VUmc
AMC
Amphia
Isala
UMCN
ASZ
Conclusion
• Both DEB and DES superior to BA in ISR
• Both DEB and DES safe in ISR
