PCI for In-Stent Restenosis. CardioVascular Research Foundation

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Felicia Parsons
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1 PCI for In-Stent Restenosis

2 ISR of BMS

3 Patterns of In-Stent Restenosis Pattern I : Focal Type IA: Articulation / Gap Type IB: Marginal Type IC: Focal body Type ID: Multifocal Pattern II,III,IV : Diffuse Pattern II : Intra-stent Pattern III: Proliferative Pattern IV : Total occlusion Mehran R. Circulation 1999;1:1872-8

4 Patterns of ISR 282 Lesions % Frequency TLR at 1 Year Focal Intrastent Proliferative Total Occusion Focal Intrastent Proliferative Total Occusion Predictors of TLR: diabetes, previous ISR and ISR patterns Mehran R. Circulation 1999;1:1872-8

5 Treatment of BMS-ISR Balloon angioplasty Cutting balloon angioplasty Rotablating atherectomy Repeat stenting Intracoronary brachytherapy Drug-eluting stent Not encouraging in diffuse ISR

6 Intracoronary Brachytherapy Most effective therapy of instent restenosis before development of DES Use of source train or balloon with beta or gamma radiation Inhibition of neo-intimal growth

7 Risk Reduction of Brachytherapy SCRIPPS WRIST Long WRIST GAMMA-I BETA-WRIST START INHIBIT PREVENT Brachytherapy Better Placebo Better

8 Trials SCRIPPS WRIST GAMMA 1 GAMMA 2 LONG WRIST B-WRIST START INHIBIT BRITE Brachytherapy Reported Clinical Trials for ISR Source 192Ir 192Ir 192Ir 192Ir 192Ir 9Y Sr/9 P32 P32 Length (mm) Pts (n) Restenosis (%) Placebo Treated

9 Paclitaxel-Coated Balloon for ISR PACCOCATH ISR Study From December 23 to July 24 Bare metal ISR (n=52) Randomization (1:1) Coated with Paclitaxel (n=26, coated-balloon group) Uncoated balloon catheter (n=26, uncoated-balloon group) 6-month angiographic late luminal loss 12-month rates of restenosis & MACE including TLR, MI, stroke, and death Scheller B. NEJM 26;355:

10 PACCOCATH ISR In-sgment Late Loss at 6 months mm 1. Coated-balloon group Uncoated-balloon group P= Scheller B. NEJM 26;355:2119

11 PACCOCATH ISR Restenosis Rate at 6 months % P< /22 1/23 Coated-balloon group Uncoated-balloon group Scheller B. NEJM 26;355:2119

12 PACCOCATH ISR 12-month Clinical Outcomes MACE including death, MI, TLR, stroke % 5 Coated-balloon group Uncoated-balloon group P=.1 Scheller B. NEJM 26;355:2119

13 First Study with SES 1-Year Clinical Event Brazil (n=25) Rotterdam (n=16) Pooled data (n=41) 15 % Death MI TLR Restenosis Tanabe K. Circulation 23;17

14 SES for Very Complex ISR % Month Results in 16 patients 4 recurrent ISR, 1 diffuse ISR, 3 total ISR /16 3/16 3/16 Death Restenosis TLR Degertekin M. JACC 23;41:184

15 % TAXUS III for ISR 2 Clinical Centers (n=28 pts) Re-Restenosis = 4 / 25 (16%) Percent diameter stenosis Proximal In-Stent Distal Post 6 Mos Tanabe K. Circulation 23;17

16 ISR of BMS DES vs. Brachytherapy

17 Treatment of IN-stent restenosis with Drug-Eluting stent versus intracoronary beta-radiation INDEED Study Seung-Jung Park, 1 Seong-Wook Park, 1 Young-Hak Kim, 1 Seung-Whan Lee, 1 Cheol Whan Lee, 1 Myeong-Ki Hong, 1 Jae-Joong Kim, 1 Bon Kwon Koo, 2 Myoung Mook Lee, 2 for the INDEED Study investigators 1 Asan Medical Center, University of Ulsan College of Medicine 2 Seoul National University Hospital

18 Study Algorithm From March 23 to July 24 Diffuse ISR (n=129) Randomization (1:1) Cutting balloon angioplasty Sirolimus-Eluting Stent (n=65, SES group) * Coronary Brachytherapy (n=64, RT group) * One patient failed to receive RT due to isotope spillage before RT 6-month angiographic and 1-year clinical follow-up

19 INDEED Lesion Length & Treated Segment mm 5 SES Radiation P=NS P=NS Lesion length Treated segment

20 INDEED QCA Analysis, Postprocedure MLD, mm SES (n=65) RT (n=64) P-value Proximal Edge In-stent Distal edge In-segment Acute gain 2.86± ± ±.6 2.3± ± ± ± ± < In-stent In-segment 1.72± ± ± ±.5 <.1.17 Values are given as n(%) and mean±sd

21 In-Hospital Outcomes INDEED Death SES (n=65) RT (n=64) P-value 1. Myocardial Infarction 1 (1.5) 2 (3.1).619 Q-MI Non Q-MI 1 (1.5) 2 (3.1) Stent thrombosis 1. TLR 1. Values are given as n(%)

22 QCA Analysis, Follow-up INDEED SES (n=49) RT (n=54) P-value F/U rate 75% 84% MLD, mm Proximal edge 2.83± ± In-stent 2.29± ±.75 <.1 Distal edge 2.64± ±.65.2 In-segment 2.17± ±.7 <.1 Values are given as n(%) and mean±sd

23 QCA Analysis, Follow-up INDEED SES (n=49) RT (n=54) P-value DS, % Proximal edge 17.55± ± In-stent 2.55± ± Distal edge 13.35± ± In-segment 25.26± ±26.42 <.1 Values are given as n(%) and mean±sd

24 QCA Analysis, Follow-up INDEED SES (n=49) RT (n=54) P-value Late loss, mm Proximal edge -.4±.34.27±.65.1 In-stent.23±.6.39± Distal edge -.3±.42.27±.64.6 In-segment.16±.57.52±.7.7 Loss index, In-segment.13±.6.43± Loss index, In-stent.12±.35.3± Values are given as n(%) and mean±sd

25 Acute Gain & Late Loss INDEED mm In-segment 1.29 SES Radiation 1 P= P=.69 Acute gain Late loss

26 Late Loss at 6 Months INDEED mm P= SES P=.1.27 Radiation P= P= In-segment Prox. edge In-stent Dist. edge

27 INDEED Restenosis Rates at 6 Months % 4 SES RT P= P= /49 16/54 3/49 11/54 In-segment In-stent

28 INDEED Clinical Outcomes at 1 Year SES (n=65) RT (n=64) P-value Death Cardiac Non-cardiac 2 (3.1) 1 (1.5) 1 (1.5).496 MI 1 (1.5) * 1. Stent thrombosis 1 (1.5) ** 1. TLR 3 (4.6) 12 (18.8).14 Cardiac death, MI, and TLR 5 (7.7) * Acute STEMI due to the occlusion of non-target vessel ** Late stent thrombosis, 6 months after the index procedure 12 (18.8). 73

29 SES vs. RT SISR Study From Feb 23 to July 24 Bare metal ISR (n=374) Randomization (2:1) Cutting balloon angioplasty Sirolimus-Eluting Stent (n=259, SES group) Coronary Brachytherapy (n=125, RT group) 9-month target vessel failure (cardiac death, myocardial infarction, target vessel revascularization Holmes D. JAMA 26;295:137-9

30 Restenosis Rates at 6 Months SISR % 4 SES RT P=.7 P=.88 Analysis-segment Injured segment Holmes D. JAMA 26;295:137-9

31 SISR 9-Month Clinical Outcomes % 3 SES RT P <.5 P <.5 P <.5 TVF MACE TLR Holmes D. JAMA 26;295:137-9

32 Six-Month Angiographic and Long-Term Outcomes after Sirolimus-Eluting Stent Implantation for Diffuse In-Stent Restenosis: Comparison with Brachytherapy AMC RT vs SES Comparison of the 6-month and 2-year outcomes of sirolimus-eluting stent implantation versus β-radiation therapy with 188 Re-MAG 3 - filled balloon for diffuse ISR in a prospective manner.

33 SES vs. Brachytherapy Diffuse ISR (n=362) Cutting or Rotablation or simple balloon AMC RT vs SES Sirolimus-Eluting Stent (n=12, SES group) * Historical control Coronary Brachytherapy (n=242, RT group) Radiation dose of 15, 18 Gy at a depth of 1. mm into the vessel wall Six-month Angiography follow-up 2-year Clinical follow-up including death, MI, TLR

34 AMC RT vs SES QCA Analysis, Baseline SES (n=12) RT (n=242) P-value Reference diameter, mm 2.98± ± Lesion length, mm 25.1± ± MLD, mm.74±.61.73±.4.38 DS, % 75.1± ±

35 AMC RT vs SES QCA Analysis, Postprocedure SES (n=12) RT (n=242) P-value MLD, mm 2.97± ±.43 <.1 DS, % -.5± ±14. <.1 Acute gain, mm 2.23± ±.54 <.1

36 AMC RT vs SES In-Hospital Outcomes SES (n=12) RT (n=242) P-value Angiographic success 1 (1) 242 (1) 1. Death 1. Myocardial infarction 1 (.8) 1 (.4) 1. Q-MI Non Q-MI 1 (.8) 1 (.4) Stent thrombosis 1. TLR 1.

37 AMC RT vs SES QCA Analysis, Follow-up SES (n=12) RT (n=242) P-value Angio F/U rate 14/12(86%) 193/242(8%) Reference, mm 2.98± ± MLD, mm 2.48± ±.79 <.1 DS, % 16.34± ±28.64 <.1 Late loss, mm.5±.55.67±.81.42

38 AMC RT vs SES Restenosis Rate at 6 Months % P<.5 9/14 51/193 SES RT

39 AMC RT vs SES Clinical Outcomes at 2 years SES (n=12) RT (n=242) P-value Death.8%.4% NS MI.8%.4% NS TLR 4.6% 13.2% <.5 One-year 4.6% 9.9% <.5 Two-year 4.6% 13.2% <.5

40 AMC RT vs SES Two-Year Clinical Outcomes MACE including death, MI, TLR % P<.5 SES RT

41 PES vs. RT TAXUS V ISR Study From June 23 to July 24 Bare metal ISR (n=396) Randomization (1:1) Cutting balloon angioplasty Paclitaxel-Eluting Stent (n=195, PES group) Beta radiation (n=21, RT group) 9-month ischemia driven target vessel revascularization Stone GW. JAMA 26;295:

42 TAXUS V ISR Baseline Characteristics TAXUS (n=195) RT (n=21) P-value Reference vessel, mm Lesion length, mm LAD lesion (%) Type C lesion (%) ISR pattern (%) -Focal Diffuse Proliferative Total occlusion Stone GW. JAMA 26;295:

43 TAXUS V ISR 9-Month Clinical Outcomes % 4 PES RT P = P = P =.2 P = TLR TVR MACE TV thrombosis 14.5 P <.1 Restenosis Stone GW. JAMA 26;295:

44 ISR of BMS SES vs. PES

45 ISAR-DESIRE SES vs PES vs POBA for ISR ISAR-DESIRE study Jun 23 ~ Oct 23 ISR (n=3) Randomization (1:1:1) SES (n=1) PES (n=1) POBA (n=1) 4% Diffuse 49% Diffuse 42% Diffuse 1-Yr F/U (n=98) CAG F/U (n=91) 1-Yr F/U (n=98) CAG F/U (n=92) 1-Yr F/U (n=99) CAG F/U (n=92) Kastrati A. JAMA 25;293:165

46 ISAR-DESIRE Restenosis and TLR Rates SES PES POBA 5% P<.1 45% P<.1 P=.19 P=.2 33% 14% 22% 19% P=.1 8% P=.2 % Restenosis TLR Kastrati A. JAMA 25;293:165

47 mm.6.5 SES vs PES In-segment Late loss of SES and PES SES PES.55 ISAR-DESIRE P=.4 Late loss Kastrati A. JAMA 25;293:165

48 DES for BMS ISR TLR in DES vs. Conventional Study DES Conventional Odds ratio Odds ratio (n/n) (n/n) (95% CI) ISAR-DESIRE 27/2 33/1.32 (.18,.57) RIBS II 8/76 22/74.28 (.11,.67) SISR 22/259 24/ (.21,.73) TAXUS-V ISR 12/195 27/21.42 (.21,.86) Total 69/73 16/5 Overall (Fixed effects).35 (.25,.49) Favors DES Favors Conventional Dibra A. JACC 27;49:616-23

49 DES for BMS ISR Composite of Death or MI Study DES Conventional Odds ratio Odds ratio (n/n) (n/n) (95% CI) ISAR-DESIRE 6/2 3/1 1. (.24, 4.8) RIBS II 3/76 3/74.97 (.19, 4.98) SISR 6/259 / (.36, ) TAXUS-V ISR 7/195 1/21.71 (.27, 1.91) Total 69/73 16/5 Overall (Fixed effects) 1.4 (.54, 2.3) Favors DES Favors Conventional Dibra A. JACC 27;49:616-23

50 DES for BMS ISR Angiographic Restenosis Study DES Conventional Odds ratio Odds ratio (n/n) (n/n) (95% CI) ISAR-DESIRE 33/183 41/92.27 (.16,.48) RIBS II 8/7 28/71.2 (.8,.48) SISR 45/227 31/15.59 (.35, 1.) TAXUS-V ISR 25/172 53/17.38 (.22,.64) Total 111/ /438 Overall (Fixed effects).36 (.27,.49) Favors DES Favors Conventional Dibra A. JACC 27;49:616-23

51 Conclusions The superiority of DES for bare-metal ISR is derived from the greater acute gain and similar to or lower late loss than that of brachytherapy. Drug-eluting stent has become the first-line therapy for bare-metal ISR replacing the brachytherapy.

52 Conclusions Among the DESs, the SES may be more effective in reducing the recurrent restenosis and improving clinical outcomes in treatment of bare-metal ISR. The superiority of SES over brachytherapy for treatment of bare-metal ISR was maintained to 2 years.

53 ISR of DES

54 TLR Rates of DES % TLR mo 1 yr 2 yr 9 mo 1 yr 2 yr 3 yr 9 mo 1 yr 2 yr 3 yr ENDEAVOR II TAXUS IV SIRIUS 1 year Outcomes in the Sirius Trial, Holmes et al, Circulation 24 1 Year Clinical Results of TAXUS IV, Stone et al, Circulation 24 2 year Outcomes in the Sirius Trial, Leon, ACC 24 2 Year Clinical Results of TAXUS IV, Stone, TCT 24 3 year Outcomes in the Sirius Trial, Leon, TCT 25 3 Year Clinical Results of TAXUS IV, Stone, ACC 25 4 year Outcomes in the Sirius Trial, Leon, TCT 26 4 yr

55 Possible Causes of DES ISR Stent under-expansion Asymmetric strut distribution Stent fracture Polymer disruption Peri-stent vessel wall injury Drug failure or resistance Polymer hypersensitivity Drug hypersensitivity

56 Morphology Patterns of ISR SIRIUS Cypher (n=31) Control (n=128) P-value I - focal 87.% (27) 42.2% (54) <.1 II/III diffuse or proliferative 6.5% (2) 5.% (64) <.1 IV - total occlusion 6.5% (2) 7.8% (1).895 Moses JW. NEJM 23;349:

57 Patterns of Cypher Restenosis SIRIUS Focal Cypher (n=31) 26 (84%) BMS (n=128) 55 (43%) P-value <.1 Diffuse 1 (3.2%) 46 (35.9%) <.1 Proliferative 2 (6.5%) 17 (13.3%).372 Total 2 (6.5%) 1 (7.8%) 1. Length of ISR, mm <.1 Aneurysm 2 (.6%) 4 (1.1%).686 Popma JJ. Circulation 24;11:3773

58 Patterns of Taxus Restenosis TAXUS-IV Taxus (n=16) BMS (n=65) P-value Focal 63 % 31 %.4 Diffuse 19 % 58 % <.1 Proliferative 6 % 8 %.11 Total 13 % 3 % 1. Length of ISR, mm Stone GW. NEJM 24;35:221

59 Restenosis Rate AMC P<.1 P=.1 % 5 4 P<.1 P< P<.1 P< P<.1 In-segment Cypher Taxus BMS P<.1 2/271 32/15 68/16 17/271 24/15 65/16 In-stent Kim YH. Catheter Cardiovasc Interv 26;67:181-7

60 Predictors of Restenosis DES subgroup AMC Variables Relative Risk 95% C.I. P-value Taxus stent <.1 Lesion length (1mm) MLD after procedure (mm) Kim YH. Catheter Cardiovasc Interv 26;67:181-7

61 Predictors of Restenosis Cypher or Taxus subgroup AMC R.R 95% C.I. P-value Cypher Multiples stent Taxus MLD after procedure (mm) Lesion length (1mm) BMS MLD after procedure (mm) Diabetes mellitus Kim YH. Catheter Cardiovasc Interv 26;67:181-7

62 Restenosis Rate AMC According to Lesion Length From Asan Medical Center % 2 15 P< < 2 2 ~ 4 > 4 mm Lee CW. Am J Cardiol 26;97:56-11

63 Drug-Eluting Stent Restenosis The Pattern Predicts the Outcome Cosgrave J, et al. JACC 26;47:2399

64 Patterns of DES ISR Of total 25 lesions in 23 patients (66.4% with SES, 33.6% with PES) - Focal ( 1mm): 65.2% - Diffuse (>1mm): 24.3% - Proliferative : 2.4% - Obstructive: 8% Pattern of restenosis associated with occurrence of ISR (OR 5.1, 95% CI 1.1~23, P=.3)and TLR (OR 3.6, 95% CI 1.2~1.9, P=.2) Cosgrave J. JACC 26;47:

65 Patterns of DES ISR Risk factors Family history Hypertension Hypercholesterolemia Current smoker Diabetes Details of DES SES PES Stent diameter Stent length Focal (n=132) 43.8% 63.4% 71.8% 16.2% 25.4% 69.9% 3.1% 2.9± ±12.6 Nonfocal (n=71) 46.4% 67.6% 71.4% 11.6% 47.9% 59.8% 4.2% 2.9± ±18.25 P-value Cosgrave J. JACC 26;47:

66 Treatment DES ISR Focal (n=132) Nonfocal (n=71) P-value Treatment Repeat DES implantation 57.1% 69%.43 POBA 3.1% 4.2%.43 Max balloon diameter (mm) 3.15± ± Max inflation pressure (mmhg) 16.35± ±3.9.8 IVUS 3.7% 34.5%.57 Cosgrave J. JACC 26;47:

67 Clinical Events Patterns of DES ISR Focal Nonfocal P-value (n=132) (n=71) Procedural/ in-hospital death - Procedural/ in-hospital CABG - Periprocedural MI 1.5% (2).54 Clinical follow-up (days) 447± ± MACE 18.9% (25) 29.6% (21).11 Cardiac death 3% (4) 4.2% (3).69 MI at follow-up 2.8% (2).12 TVR (per patient) 15.9% (21) 22.5% (16).25 TLR (per patient) 11.4% (15) 22.5% (16).4 TVR (per lesion) 14.7% (24) 23.% (2).12 TLR (per lesion) 9.8% (16) 23.% (2).7 Cosgrave J. JACC 26;47:

68 Treatment of DES failure Very little information about the results of Published data on randomized trials Registry data including more than 1 patients Balloon angioplasty Cutting balloon angioplasty Repeat stenting Debulking Intracoronary brachytherapy Drug eluting stent

69 % 2 Focal SES Restenosis Target lesion revascularization 17.1 N= P= POBA is likely the most cost effective treatment of focal SES-stenosis POBA DES Melzi G. Am J Cardiol 25;96(suppl 7A): 188H

70 Brachytherapy for DES Restenosis RESCUE registry 6-month clinical follow-up All MACE Death Q-wave MI Non Q-wave MI TVR TLR Subacute thrombosis Late thrombosis 2 (4.%) () () 2 (4.%) 2 (4.%) 2 (4.%) () () RT as adjunct therapy to PCI for ISR of a DES is safe. Torguson R. Circulation 25;112 (Suppl 17): II-519

71 Repeated DES for DES ISR Variable Pattern of Restenosis Focal Nonfocal Diffuse Proliferative Occlusive Treatment of DES restenosis SES implantation PES implantation DCA IVUS Cutting balloon Stent length (mm) Same DES (n=17) 72.9% (78) 27.1% (29) 19.6% (21) 5.6% (6) 1.9% 92) 72% (77) 28% (3) 3.7% (4) 25.2% (27) 6.5% (7) 22.17±12.3 Different DES (n=94) 5% (47) 5% (47) 34% (32) 16% (15) 48.9% (46) 51.1% (48) 7.4% (7) 42.6% (4) 2.1% (2) 25.8±12.9 P-value Cosgrave J. Am Heart J 27;153:354-9

72 Repeated DES for DES ISR Variable Procedural MI Acute thrombosis Follow-up Total death Cardiac death MI TLR (per patient) TVR (per patient) Major adverse cardiac events CABG Angiographic follow-up Clinical Events Same DES (n=96) 2.1% (2) Different DES (n=78) 1.3% (1) P-value % (3) % (3).25 1% (1) % (16) 16.7% (13) % (2) 17.9% (14).7 26% (25) 17.9% (14).27 1% (1) % (64) 67.5% (52) 1. Cosgrave J. Am Heart J 27;153:354-9

73 Repeated DES for DES ISR Variable Focal DES restenosis Diabetes mellitus Angio follow-up lesions TLR (per lesion) TVR (per lesion) Restenosis Nonfocal DES restenosis Diabetes mellitus Angio follow-up lesions TLR (per lesion) TVR (per lesion) Restenosis Same DES (n=17) % (21) 71.4% (55) 12.8% (2) 19.2% (15) 2% (11) % (17) 6.7% (17) 24.1% (7) 24.1% (7) 47.1% 98) Different DES (n=94) 47 17% (8) 78.3% (36) 8.5% (4) 12.8% (6) 13.9% (5) % (15) 63.8% (3) 23.4% (11) 23.4% (11) 4% (12 P-value Cosgrave J. Am Heart J 27;153:354-9

74 SES for SES Restenosis % 1 Asian Multicenter Registry 156 pts (198 lesions): 1 year follow-up MACE at 1m MACE at 12m TLR Restenosis The use of SES in SES-ISR was safe with low complication and low incidence of restenosis. Nakamura S. Circulation 25;112(Suppl 17A): II-736

75 AMC Angiographic Restenosis No. of ISR Length of ISR SES PES P=.31 P=.31 P=.16 Number of ISR Length (mm) Focal Diffuse Kim YH. Circulation 26;114:

76 TLR for SES Restenosis in SIRIUS 27 TLRs (5%) from 533 patients Bypass surgery 4 (14.8%) Repeat PCI 23 (85.2%) BMS 2 (87.%) Balloon 2 (8.7%) Brachytherapy 1 (4.3%) Recurrent TLR for 2 years 6 (26%) BMS 2 Balloon 1 Brachytherapy 3 Moses JW. Am J Cardiol 24;supple 6A:13E

77 Registry of Repeat PCI for SES Restenosis Lesion characteristics at index procedure 24 pts (27 lesions) De novo lesion Balloon restenosis In-stent restenosis Brachytherapy failure 7% 4% 15% 11% Lemos PA. Circulation 24;19: 25-2

78 Registry of Repeat PCI for SES Restenosis Methods of PCI 24 pts (27 lesions) Balloon dilatation 11% Bare-metal stenting Repeated SES implantation PES implantation Mean lesion length, mm Total length of repeat stenting, mm 4% 44% 41% 11.2 ( ) 17(8-3) Lemos PA. Circulation 24;19: 25-2

79 Registry of % Repeat PCI for SES Restenosis 5 Restenosis Rates (median 281 days) (TLR: 2.8%, Event-free survival : 7.2% during 279 days) Overall SES/PES SES PES Lemos PA. Circulation 24;19: 25-2

80 Registry of Repeat PCI for SES Restenosis Predictors of recurrent restenosis Hypercholestrolemia Previous angioplasty at index procedure Failed brachytherapy SES failure treated with balloon dilatation Needing treatment before 6 months from index procedure 69% vs. %, P<.1 67% vs. 11%, P=.2 1% vs. 33%, P=.6 1% vs. 33%, P=.6 1% vs. 25%, P<.1 Lemos PA. Circulation 24;19: 25-2

81 Repeated PCI for DES ISR AMC Registry CTO (> 3m) ISF of BMS Ostial Bifurcation stenting Use of SES Location LM LAD LCX RCA Total stent length (mm) SES (n=33) (42.4%) 2 (6.1%) 23 (69.7%) 1 (3.%) 7 (21.2%) 32.2 ± 15.6 Conventional (n=25) (52%) 1 (4.%) 15 (6.%) 1 (4.%) 8 (32.%) 4.2 ± 2.4 P-value Conventional treatment: cutting balloon in 11 lesions and brachytherapy in 14 lesions

82 AMC DES ISR Angiographic Characteristics SES (n=33) Conventional (n=25) P-value ISR classification Focal Diffuse Proliferative Total Location of restenosis Edge Intra-stent LL, mm RVD, mm MLD, mm Before procedure After procedure Acute gain, mm 18 (54.9%) 5 (15.2%) 7 (21.2%) 3 (9.1%) 25 (75.8%) 17 (51.5%) 14. ± ± ± ± ±.5 9 (36.%) 8 (32.%) 7 (28.%) 1 (4.%) 9 (36.%) 25 (1.%) 15.3 ± ± ± ± ± < <.1 <.1

83 Follow-up MLD and Late Loss AMC DES ISR mm 5 4 SES Conventional P < MLD Late LL

84 AMC DES ISR Restenosis Rate at 6 Months % SES P=.1 Conventional

85 Outcomes of IVUS Follow-up AMC DES ISR mm P=NS SES Conventional P=NS P=NS 8.37 P=NS P<.6 EEM Stent Lumen P&M Intimal hyperplasia.89 1

86 Subgroup Analysis of Recurrent Restenosis Rates AMC DES ISR Edge Intra-stent Type I Variables Used stent at the index procedure Sirolimus-eluting Paclitaxel-eluting Location of restenosis Pattern of restenosis Type II, III, and IV SES /12 (%) /15 (%) /22 (%) /12 (%) /16 (%) /11 (%) Conventional 2/11 (18.2%) 5/9 (55.6%) 4/7 (57.1%) 7/2 (35.%) 3/8 (37.5%) 4/12 (33.3%) P-value

87 Randomized Trials of ISR

88 DIFFUSE Type In-Stent Restenosis after Drug-Eluting Stents Implantation Treated by Additional Drug-Eluting Stents: Sirolimus- Eluting Stent vs. Paclitaxel-Eluting Stent and vs. Zotarolimus-Eluting Stent

89 AMC DIFFUSE-ISR 3 Trial Diffuse Type In-Stent Restenosis (Lesion Length 1mm) After Drug-Eluting Stent Implantation (Total 3 patients) 1:1:1 randomization CYPHER (n=1) ENDEAVOR (n=1) TAXUS Liberte (n=1) Clinical and angiographic follow-up at 9 months Primary end point: (1) Binary angiographic restenosis at 9 months

90 FOcal In-stent Restenosis after Drug-Eluting Stent Implantation Treated by CUtting Balloon Angioplasty versus Sirolimus- Eluting Stent

91 AMC FOCUS Trial Focal In-Stent Restenosis (Lesion Length 1mm) After Drug-Eluting Stent Implantation (Total 2 patients) 1:1 randomization Sirolimus-Eluting Stent (n=1) Cutting balloon (n=1) Clinical and Angiographic follow-up at 9 months Primary end point: (1) Binary angiographic restenosis at 9 months

92 Conclusions The effective treatment of ISR within DES has not been sufficiently studied. Up to now, the effectiveness of conventional angioplasty for the focal ISR after DES may be acceptable and comparable to repeat DES implantation.

93 Conclusions Repeat DES treatment with same or different antiproliferative agents appears to be effective treatment option for DES failure Further larger trial is needed for delineating the role of DES, conventional treatment or brachytherapy for treatment of DES failure.

94 Recommended Strategy to Treat DES ISR DES ISR IVUS is recommended to identify mechanical problems Focal POBA, scoring balloons, Another DES? Diffuse Another DES if Brachytherapy not available Focal at edges Another DES

In-Stent Restenosis. Can we kill it?

In-Stent Restenosis. Can we kill it? In-Stent Restenosis Can we kill it? However, In-stent Restenosis is the most serious problem (2-25%) More than 15, lesions will need treatment because of in-stent restenosis. Varying Prevalence Rates of