Restenosis - Capodanno CardioLucca, November 28, 2014 Slide 1 Autumn in Lucca V Simposio - 28 Novembre 2014 4.30PM-4.45PM L incubo del paziente e le incognite del cardiologo: la restenosi intrastent resta un problema fisiopatologico ancora irrisolto? Davide Capodanno, MD, PhD Associate Professor, University of
Restenosis - Capodanno CardioLucca, November 28, 2014 Slide 2 Utilization of Stent Type and In-Stent Restenosis 10,004 PCI patients with follow-up angiography from the DHZ Restenosis registry First Generation DES: 8/2002-12/2005 Second Generation DES: from 1/2006 Restenosis First Generation DES Second Generation DES Cassese S. et al. Heart. 2014;100:153-9
Restenosis - Capodanno CardioLucca, November 28, 2014 Slide 3 Prognostic Role of In-Stent Restenosis 10,004 PCI patients with follow-up angiography from the DHZ Restenosis registry (26.4% ISR) Predictors of 4-year mortality HR 95% CI P value Restenosis at routine control angiography 1.23 1.03-1.46 0.02 Age (for each 10-year increase) 2.34 2.12-2.60 <0.001 Diabetes mellitus 1.68 1.41-1.99 <0.001 Current smoking habit 1.39 1.09-1.76 0.01 Left ventricular ejection fraction (for each 5% decrease) 1.39 1.31-1.48 <0.001 Female gender 0.73 0.60-0.88 <0.001 The impact of restenosis was confirmed in asymptomatic patients undergoing routine control angiography. Mortality was not impacted by the decision to perform TVR Cassese S. et al. Eur Heart J. 2014 [Epub ahead of print]
Restenosis - Capodanno CardioLucca, November 28, 2014 Slide 4 Restenosis: Angiographic Definition Restenosis Recurrent diameter stenosis >50% at the stent segment or its edges (5-mm segments adjacent to the stent) Mehran R, et al. Circulation. 1999;100:1872-1878
Restenosis - Capodanno CardioLucca, November 28, 2014 Slide 5 OCT: New Avenues for Tissue Characterization Homogeneous bright neointimal proliferation Uniform neointimal proliferation with microvessels Layered pattern with multiple microvessels in the dark layer overlying the stent struts Multilayered pattern Alfonso F, et al. J Am Coll Cardiol. 2014;63:2659-73
Restenosis - Capodanno CardioLucca, November 28, 2014 Slide 6 BMS-ISR and DES-ISR: Different Entities? Magnification images of restenosis within BMS and a DES, both implanted 5 years antemortem smooth muscle cell-rich neointimal hyperplasia neoatherosclerosis with formation of a necrotic core chronic inflammation with neovascularization around stent struts neoatherosclerosis with calcification BMS DES Joner M, CVPath Inc., Gaithersburg, Maryland
Restenosis - Capodanno CardioLucca, November 28, 2014 Slide 7 Features of Restenotic Tissue in BMS and DES Imaging features BMS restenosis DES restenosis Angiographic morphology Diffuse pattern more common Focal pattern more common OCT tissue properties Homogeneous, high-signal band most common Layered structure or heterogeneous most common Time course of late luminal loss Late loss maximal by 6-8 months Ongoing late loss out to 5 years Histopathological features Smooth muscle cellularity Rich Hypocellular Proteoglycan content Moderate High Peri-strut fibrin and inflammation Occasional Frequent Complete endothelialization 3-6 months Up to 48 months Thrombus present Occasional Occasional Neoatherosclerosis Relatively infrequent, late Relatively frequent, accelerated Alfonso F, et al. J Am Coll Cardiol. 2014;63:2659-73
Restenosis - Capodanno CardioLucca, November 28, 2014 Slide 8 Underlying Mechanisms of Restenosis 1. Stent underexpansion Underdeployment due to undersizing Underlying heavily calcified lesion 2. Geographical missing ( candy wrapper restenosis) Stent misplacement Stents not fully covering the underlying lesion 3. Stent fracture 4. Drug resistance and local hypersensitivity reactions Alfonso F, et al. J Am Coll Cardiol. 2014;63:2659-73
Restenosis - Capodanno CardioLucca, November 28, 2014 Slide 9 Management Strategies for ISR Conventional angioplasty Cutting and scoring therapy Debulking techniques Vascular Brachiterapy Repeat Stenting Drug-coated angioplasty
Restenosis - Capodanno CardioLucca, November 28, 2014 Slide 10 Management Strategies for ISR Conventional angioplasty Cutting and scoring therapy Debulking techniques Vascular Brachiterapy Repeat Stenting Drug-coated angioplasty
Restenosis - Capodanno CardioLucca, November 28, 2014 Slide 11 Plain Old Balloon Angioplasty (POBA) 1. Technically straigthforward 2. Satisfactory acute results, particularly in focal patterns, but high long-term restenosis rates 3. Technique Review the index procedure Favors noncompliant s to avoid dog bone effects, with a 1.1:1 -to-artery ratio. Target the narrowing rather than the entire stented segment Avoid slippage outside the stent ( watermelon seeding phenomenon) 4. Outdated
Restenosis - Capodanno CardioLucca, November 28, 2014 Slide 12 Management Strategies for ISR Conventional angioplasty Cutting and scoring therapy Debulking techniques Vascular Brachiterapy Repeat Stenting Drug-coated angioplasty
Restenosis - Capodanno CardioLucca, November 28, 2014 Slide 13 Cutting Standard catheter with lateral blades Offers protection against watermelon seeding, anchoring the within the target lesion, preventing slippage related problems Deeply incises neointimal tissue and, at least theoretically, may favor subsequent extrusion Superior than POBA in reducing slippage and need for unplanned stent implantation (RESCUT trial)
Restenosis - Capodanno CardioLucca, November 28, 2014 Slide 14 Scoring (Angiosculpt) Nitinol scoring element with three spiral struts that wrap around the OCT Image ISR Lesion Prior- and Post- AngioSculpt demonstrating scoring Takano et al. Int J Cardiol. 2010;141:51-3
Restenosis - Capodanno CardioLucca, November 28, 2014 Slide 15 Scoring ballons in DES-ISR treated with DCB ISAR-DESIRE 4 N=250 Patients undergoing DCB angioplasty of DES-ISR R 1:1 Scoring ballon + DCB DCB alone Primary Endpoint In-segment percent diameter stenosis at 6-8 months follow-up angiography Estimated Study Completion Date: December 2015 NCT01632371
Restenosis - Capodanno CardioLucca, November 28, 2014 Slide 16 Management Strategies for ISR Conventional angioplasty Cutting and scoring therapy Debulking techniques Vascular Brachiterapy Repeat Stenting Drug-coated angioplasty
Restenosis - Capodanno CardioLucca, November 28, 2014 Slide 17 Debulking Techniques Excimer Laser Showed good results in selected cases but eventually proved to have poorer ablation capability compared with rotational atherectomy 1 Rotational atherectomy Failed to show benefit compared with angioplasty alone in BMS-ISR (ARTIST trial). May still be required as a bailout strategy in patients with undilatable ISR lesions 2 1 Mehran R, et al. Circulation 2000;101:2484 9 2 Von Dahl J, et al. Circulation 2002;105:583 8
Restenosis - Capodanno CardioLucca, November 28, 2014 Slide 18 Management Strategies for ISR Conventional angioplasty Cutting and scoring therapy Debulking techniques Vascular Brachiterapy Repeat Stenting Drug-coated angioplasty
Restenosis - Capodanno CardioLucca, November 28, 2014 Slide 19 Brachytherapy versus DES for BMS-ISR SIRS: 384 patients with BMS-ISR 2:1 randomized to vascular brachytherapy or SES TAXUS V ISR: 396 patients with BMS-ISR 1:1 randomized to vascular brachytherapy or PES Angiographic restenosis at Follow-up P=0.07 P<0.001 Holmes Dr Jr et al, JAMA 2006;295:1264 73 Stone GW, et al, JAMA 2006;295:1253 63
Restenosis - Capodanno CardioLucca, November 28, 2014 Slide 20 Management Strategies for ISR Conventional angioplasty Cutting and scoring therapy Debulking techniques Vascular Brachiterapy Repeat Stenting Drug-coated angioplasty
Restenosis - Capodanno CardioLucca, November 28, 2014 Slide 21 POBA versus BMS for BMS-ISR RIBS: 450 patients with BMS-ISR randomized to POBA or sandwich BMS After the procedure Stent (N=224) POBA (N=226) P value Minimal lumen diameter (mm) 2.77±0.4 2.25±0.5 <0.001 Stenosis (% of lumen diameter) 12±10 23±10 <0.001 Acute gain (mm) 2.08±0.5 1.58±0.5 <0.001 After the procedure ( in-lesion ) Minimal lumen diameter (mm) 1.69±0.8 1.54±0.7 0.046 Stenosis (% of lumen diameter) 43±24 45±23 0.31 Restenosis (%) 33% 38% 0.36 Late loss (mm) 1.06±0.7 0.72±0.7 <0.001 In patients with large vessels ( 3 mm) and restenosis located at the stent edge, stenting exhibited better results Alfonso F, et al. J Am Coll Cardiol 2003;42:796 805
Restenosis - Capodanno CardioLucca, November 28, 2014 Slide 22 POBA versus DES for BMS-ISR ISAR-DESIRE: 300 patients with BMS-ISR randomized to POBA, SES or PES RIBS 2: 150 patients with BMS-ISR randomized to POBA or PES Target vessel revascularization at 9 months P<0.0001 P=0.03 Kastrati A, et al. JAMA 2005;293:165 71 Alfonso F. J. Am Coll Cardiol 2006;47:2152-60
Restenosis - Capodanno CardioLucca, November 28, 2014 Slide 23 Same DES versus Switch DES for DES-ISR ISAR-DESIRE 2: 450 patients with SES-ISR randomized to SES or PES P=0.69 P=0.52 Mehilli J. Et al. J Am Coll Cardiol 2010;55:2710 6
Restenosis - Capodanno CardioLucca, November 28, 2014 Slide 24 Bioresorbable Scaffolds for DES-ISR? Rationale The device should eventually disappear from the vessel wall, avoiding the presence of multiple stent layers ( onion skin ) Unkowns Lumen crowding due to strut thickness Device flexibility that may affect access to restenotic lesions Questions regarding radial strength and recoil Alfonso F, et al. J Am Coll Cardiol 2014;63:2875
Restenosis - Capodanno CardioLucca, November 28, 2014 Slide 25 Management Strategies for ISR Conventional angioplasty Cutting and scoring therapy Debulking techniques Vascular Brachiterapy Repeat Stenting Drug-coated angioplasty
Restenosis - Capodanno CardioLucca, November 28, 2014 Slide 26 DCB versus EES for BMS-ISR RIBS V: 189 patients with BMS-ISR randomized to DCB or EES Minimum Lumen Diameter at Follow-up P<0.0001 P<0.0001 Binary restenosis and clinical events at 1 year were low and similar in both groups Alfonso F., et al. J Am Coll Cardiol 2014;63:1378 86
Restenosis - Capodanno CardioLucca, November 28, 2014 Slide 27 DCB versus PES versus POBA for DES-ISR ISAR DESIRE 3: 402 patients with BMS-ISR randomized to DCB or EES Cumulative Frequency (%) 100 80 60 40 20 0 PEB 38.0% PES 37.4% PEB versus PES P non-inferiority =0.007 Paclitaxel-Eluting Balloon (PEB) Paclitaxel-Eluting Stent (PES) Balloon Angioplasty (BA) 0 20 40 60 80 100 Diameter Stenosis at Follow-up Angiography (%) PEB versus BA PES versus BA P superiority <0.001 BA 54.1% Byrne RA, et al. Lancet 2013;381:461 7
Restenosis - Capodanno CardioLucca, November 28, 2014 Slide 28 DCB versus EES for DES-ISR RIBS IV: 189 patients with BMS-ISR randomized to DCB or EES Minimum Lumen Diameter at Follow-up P=0.004 P<0.001 EES also provided better late clinical results, driven by a significant reduction in TLR Alfonso F., et al. TCT 2014, Washington DC
Restenosis - Capodanno CardioLucca, November 28, 2014 Slide 29 2014 ESC/EACTS Guidelines on myocardial revascularization Management of restenosis Repeat PCI is recommended, if technically feasible. I C DES are recommended for the treatment of in-stent re-stenosis (within BMS or DES). Drug-coated s are recommended for the treatment of in-stent restenosis (within BMS or DES). IVUS and/or OCT should be considered to detect stent-related mechanical problems. I I IIa A A C Windecker et al. Euro Heart J 2014 [Ahead of print]
Restenosis - Capodanno CardioLucca, November 28, 2014 Slide 30 Closing Remarks / 1 1. Although the advent of DES has reduced the incidence of ISR, treatment of this clinical entity remains a prevailing clinical problem. 2. The substrate of ISR encompasses a pathological spectrum ranging from smooth muscle cell proliferation to neoatherosclerosis. 3. Intracoronary imaging provides unique insights into the underlying etiology of ISR, but its role in optimizing the clinical results of these reinterventions still remains unsettled.
Restenosis - Capodanno CardioLucca, November 28, 2014 Slide 31 Closing Remarks / 2 4. Among currently available therapeutic modalities, DES and DCB provide the best clinical and angiographic results in patients with ISR In a fast-evolving field, second generation DES were recently found to be better than DCB for DES-ISR in RIBS IV DCB may be preferred over DES in patients with ISR and multiple metal layers, in those with large side branches, and in those at high bleeding risk undergoing prolonged dual antiplatelet therapy. 5. CABG should be considered for frequent flyers patients, although this will usually be dictated by the prognostic relevance of the restenotic lesion. dcapodanno@gmail.com