In-stent restenosis - NVHVV CarVasZ 2014/S24_1_K_Boerlage_van_Dijk.pdfBalloon in In-Stent Restenosis Klinik für Innere Medizin III, Universitätsklinikum des Saarlandes, Homburg

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

Thank you for your attention

[email protected]

[email protected]