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/mm 2 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
DES Equal Drug Distribution with DEB Hwang, Circulation 2001; 104: 600-5 SeQuent Please
PACCOCATH ISR I and II A Prospective, Randomized Trial of a Paclitaxel-Eluting Balloon in In-Stent Restenosis PI: Bruno Scheller Klinik für Innere Medizin III, Universitätsklinikum des Saarlandes, Homburg / Saar, Germany
PACCOCATH ISR I and II A Prospective, Randomized Trial of a Paclitaxel-Eluting Balloon in In-Stent Restenosis PI: Bruno Scheller Klinik für Innere Medizin III, Universitätsklinikum des Saarlandes, Homburg / Saar, Germany
PACCOCATH ISR I/II 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
Late lumen loss - ISR I vs. ISR II 1.8 1.6 Uncoated balloon Drug-coated balloon 1.4 1.2 p < 0.01 p < 0.01 [mm] 1.0 0.8 p < 0.01 p < 0.01 0.6 0.4 0.2 0.0 late loss in-stent ISR I late loss insegment ISR I late loss in-stent ISR II late loss insegment ISR II 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
PEPCAD II Freedom from stent thrombosis, target lesion revascularization, myocardial infarction, and death B No. at risk Drug-coated balloon 70 70 67 65 64 63 62 Drug-eluting stent 60 58 56 53 47 47 46 19
ISAR-DESIRE 3 ISAR-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 Endpoint Diameter Stenosis at Follow-up Angiography
Secondary Endpoint Binary Restenosis Target Lesion Revascularization
ISAR-DESIRE 3 RIBS V A randomized comparison of DEB vs EES in patients with BMS ISR Alfonso F. et al. JACC 2014; 1378-86
ISAR-DESIRE 3 The 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 Isala ASZ UMCN Amphia
Conclusion Both DEB and DES superior to BA in ISR Both DEB and DES safe in ISR
Thank you for your attention k.boerlage-vandijk@olvg.nl k.boerlage-vandijk@amc.uva.nl