Stent Thrombosis in Coronary Bifurcation After DES Implantation

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1 Welcome to the 5 th European Bifurcation Club September BERLIN Stent Thrombosis in Coronary Bifurcation After DES Implantation Insight From J-Cypher Registry and Asian Multicenter Registry

2 Sunao Nakamura FACC, FAHA, FESC, FSCAI Department of Cardiology : New Tokyo Hospital Department of Advanced Cardiovascular Medicine : Kumamoto University Takeshi Kimura MD. Toshihiro Tamura MD. Kazuaki Mitsudo MD. Takeshi Morimoto MD. Kazushige Kadota MD. Kyoto University Hospital Kyoto University Hospital Kurashiki Central Hospital Kyoto University Hospital Kurashiki Central Hospital On behalf of the j-cypher Registry Investigators

3 J-Cypher Paticipating Centers Ehime Prefectural Central Hospital Ogaki Municipal Hospital Osaka City General Hospital Osaka Red Cross Hospital Saiseikai Noe Hospital Kanazawa Cardiovascular Hospital Shonan Kamakura General Hospital Kawasaki Social Insurance Hospital Tokusyukai Kisiwada Hospital National Hospital Organization Kyusyu Cardiovascular Center Kyoto University Hospital Kyoto second Red Cross Hospital Kurashiki Central Hospital Gunma Prefectural Cardiovascular Center Noto General Hospital Kokura Memorial Hospital National Cardiovascular Center Saiseikai Kumamoto Hospital Saitama Prefectural Cardiovascular Hospital Sizuoka General Hospital Shinkoga Hospital Shinbeppu Hospital Sendai Kousei Hospital Tsuchiya General Hospital Teikyo University Hospital Tokushima Red Cross Hospital Tominaga Hospital Toyohashi Higashi Hospital Nanpuh Hospital Fukuoka University Hospital Fukuyama Cardiovascular Hospital Banbuntane Hotokukai Hospital Hokuto Cardiovascular Hospital Hokkou Memorial Hospital Maizuru Kyosai Hospital Matsue Red Cross Hospital Mie Heart Center Miyazaki Ishikai Hospital Wakayama Red Cross Hospital The j-cypher Registry

4 -Multicenter Registry in Asia- New Tokyo Hospital Damansara Heart Center Konyang University Hospital Husada Hospital Chest Disease Institute Her Majesty's Cardiac Center, Siriraj Hospital King Chulalongkorn Memorial Hospital Sunao Nakamura M.D, Ph.D. (Japan) Tamil Selvan Muthusamy M.D. (Malaysia) Jang-Ho Bae M.D. (Korea) Yeo Hans Cahyadi M.D. (Indonesia) Sudaratana Tansuphaswadikul M.D. (Thailand) Damras Tresukosol M.D. (Thailand) Wasan Udayachalerm M.D. (Thailand) ESC 2008

5 Stent Thrombosis in Japanese/Asian 1. Low Incidence of Stent Thrombosis J-Cypher and Asian Multicenter Registry The j-cypher Registry

6 Stent Thrombosis in J-Cypher Registry 0.05 ARC Definite Between 30 Days and 3 Years Slope 0.28% / Year Follow-up interval (Days) 30 Days 1 Yr. 2 Yrs. 3 Yrs. Cumulative incidences 0.36% 0.61% 0.84% 1.18% n of pts at risk 12,824 12,625 11,843 9,036 4,191 # Events: Not yet fully adjudicated

7 Definite Stent Thrombosis Bern/Rotterdam vs j-cypher Bern / Rotterdam PES SES Between 30 Days and 3 Years Slope 0.5% / Year j-cypher Between 30 Days and 3 Years Slope 0.28% / Year Bern / Rotterdam Incidence, SES (%) Incidence, Patients PES at Risk (%)(n) Patients at risk (n) j-cypher Cumulative Incidence (%) Patients at Risk (n) Daemen J., et al., Lancet 2007; 369:

8 Stent Thrombosis to 5 Years -Asian Multicenter Registry- ARC Definite / Probable BMS vs DES SES vs PES 2.0 % 2.0 % 1.5 BMS DES 1.5 SES PES Time (months) SAT 0.5%, LAST 0.18%/year Time (months)

9 Stent Thrombosis in Japanese 2. Predictor of Stent Thrombosis Multivariate Analysis of Early ST and Late/Very Late ST The j-cypher Registry

10 Predictors of Early ST Multivariable analysis Early ST in 43 lesions among 17,050 lesions treated exclusively by Cypher Factors R.R. 95%C.I. P Value Emergency procedure (ACS) 1.88 ( ) 0.02 Male gender 1.45 ( ) 0.09 LVEF 40% 1.29 ( ) 0.23 Those variables with p value <0.1 in the univariable analysis were incorporated into the multivariable model. STEMI was excluded from the final model.

11 Stent Thrombosis in STEMI 0.02 ARC Definite Log rank p= STEMI 0.01 Others Follow-up interval (Days) 30 Days 1 Yr. 2 Yrs. 3 Yrs STEMI 0.76% 1.01% 1.21% 1.37% 1,321 1,269 1, Others 0.2% 0.36% 0.51% 0.73% 18,354 18,108 17,013 13,013 6,001

12 Predictors of LST / VLST Multivariable analysis LST / VLST in 67 lesions among 16,801 lesions treated exclusively by Cypher Factors R.R. 95%C.I. P Value Hemodialysis 1.91 ( ) ESRD (e-gfr < 30/Non-HD) 1.81 ( ) Two stents for bifurcation 1.81 ( ) 0.01 Those variables with p value < 0.1 in the univariable analysis were incorporated into the multivariable model.

13 Stent Thrombosis in Japanese 3. Discontinuation of Anti-platelet Therapy and Timing of Stent Thrombosis The j-cypher Registry

14 0.5 Surgery During Follow-up Cumulative Incidence Follow-up interval (Days) 30 Days 6 Mos. 1 Yr. 2 Yrs. 3 Yrs n of pts 0.3% 2.0% 4.2% 8.6% 12.8% at risk ,607 12,062 11,289 3, Excluding endovascular treatment and CABG

15 Discontinuation of Anti-platelet Therapy and Timing of Stent Thrombosis 1 All Stent Thrombosis 0.5 ST within 30 Days after Discontinuation of APT Incidence of stent thrombosis Incidence of stent thrombosis 0.4 From 0.3 around 7 Days Later Days after discontinuation of anti-platelet therapy Days after discontinuation of anti-platelet therapy Days after discontinuation Cumulative incidence 23% 40% 67% 85% Number of events Number of patients at risk Days after discontinuation Cumulative incidence 4% 15% 19% 21% Number of events Number of patients at risk

16 Stent Thrombosis in Japanese 4. Role of Thienopyridine 6 months after Implantation of DES The j-cypher Registry

17 Anti-platelet Therapy Discontinuation Stent Thrombosis and Discontinuation of Aspirin and/or Thienopyridine Incidence of Definite Stent Thrombosis Discontinuation of both thienopyridine and aspirin, but not discontinuation of thienopyridine therapy alone, was associated with an increased risk of ST

18 6-Month Landmark Analysis Landmark analysis did not suggest an apparent clinical benefit of thienopyridine use beyond 6 months after SES implantation

19 Left Main Substudy From J-Cypher Registry Comparing 1. Bifur. vs Non Bifur. 2. One Stent vs Two Stent The j-cypher Registry

20 Left Main Substudy from the j-cypher Registry j-cypher registry (August 2004-November 2006) patients with first registration Main-Analysis 582 patients underwent PCI for ULMCA (4.5% of whole population) Vs patients underwent PCI for non-ulmca Patients excluded: 74 patients with non-ses treatment for ULMCA (non-stent, BMS or other type of DES) Patients excluded: 28 patients with hybrid treatment for ULMCA (SES and BMS or other type of DES) Patients excluded: 4 patients missing information on lesion location of ULMCA or bifurcation stent strategy Sub-Analysis 476 patients treated exclusively with SES for ULMCA Toyofuku M, et al. Circulation 2009 in press.

21 Left Main Substudy from the j-cypher Registry Baseline and Procedural Characteristics ULMCA Non-ULMCA P (n=582) (n=12242) Bifurcation lesion 81% 24% <.0001 Bifurcation 2 stents 30% 4.6% <.0001 N of vessels treated 1.9± ±0.5 <.0001 Extent of CAD <.0001 LMCA only 6.9% 0% LMCA + 1 vessel 24% 48% LMCA + 2 vessels 40% 30% LMCA + 3 vessels 21% 15% Post CABG 7.9% 7.1% Total stent length (mm) 56.3± ±27.6 <.0001 IVUS use 63% 47% <.0001

22 Left Main Substudy from the j-cypher Registry 1 Unadjusted Survival 90.8% 85.4% 1 Adjusted Survival 93.9% 92.6% Survival P < Non-ULMCA ULMCA Survival P =0.12 Non-ULMCA ULMCA Days after stent implantation Interval(Days) Non-ULMCA Incidence (%) No. at risk ULMCA Incidence (%) No. at risk Days after stent implantation Interval(Days) Non-ULMCA Incidence (%) ULMCA Incidence (%)

23 Lesion Location and Clinical Outcome Ostial / Shaft versus Bifurcation Survival (A) Cardiac Mortality P=0.41 Ostial/shaft Lesion Distal Bifurcation Lesion 92.4% 90.2% Freedom from TLR (B) Target Lesion Revascularization Bifurcation Lesion!! P= Ostial/shaft Lesion Distal Bifurcation Lesion 96.4% 82.9% Days after stent implantation Interval (Days) Ostial/Shaft Incidence (%) No. at risk Distal Bifurcation Incidence (%) No. at risk Days after stent implantation Interval (Days) Ostial/Shaft Incidence (%) No. at risk Distal Bifurcation Incidence (%) No. at risk

24 Bifurcation Strategies and Clinical Outcome One-stent versus Two-stents (A) Cardiac Mortality (B) Target Lesion Revascularization % 1 Survival Two Stent!!! 87.8% P=0.018 Bifurcation One Bifurcation Two Freedom from TLR Two Stent!!! P< Bifurcation One Bifurcation Two 69.1% 88.9% Days after stent implantation Day Bifurcation One Incidence (%) No. at risk Bifurcation Two Incidence (%) No. at risk Days after stent implantation Day Bifurcation One Incidence (%) No. at risk Bifurcation Two Incidence (%) No. at risk

25 Bifurcation Substudy From J-Cypher Registry Predictor of Target Lesion Revascularization in Elective Two-Stent Technique The j-cypher Registry

26 Bifurcation stenting strategy 2250 Bifurcation lesions Provisional stenting N=1978 (87.8%) Crossover Elective stenting N=272 (12.1%) ( 4.5% ) 272 One stenting N=1889 (84.0%) Two stenting N=361 (16.0%) The j-cypher Registry

27 Strategy of Elective Two-stent approach Provisional : 1978 Crush technique 26.8% Kissing 5.1% Elective : 272 Culotte technique 15.4% T-Stenting 52.6% The j-cypher Registry

28 Cumulative incidence of Definite Stent Thrombosis (%) 3.0 Incidence of stent thrombosis 2.0 á Days after stent implantation Days after stent implantation Cumulative incidence % % % Number of events The j-cypher Registry

29 Multivariate Analysis for the Predictors of TLR TLR Postprocedural main vessel reference diameter Odds ratio (95% C.I.) 0.08 ( ) P Value Total stent length Crush stenting 1.03 ( ) 3.10 ( ) Two stent in Cx lesion Postprocedural side branch reference diameter 1.69 ( ) 6.18 ( ) The j-cypher Registry

30 Bifurcation Substudy From J-Cypher Registry Role of Final Kissing Balloon Technique in Single Main Branch Stenting The j-cypher Registry

31 Bifurcation stenting strategy 2250 Bifurcation lesions Provisional stenting N=1978 (87.8%) Crossover Elective stenting N=272 (12.1%) ( 4.5% ) 272 One stenting N=1889 (84.0%) Two stenting N=361 (16.0%) The j-cypher Registry

32 Multivariate Analysis for the Predictors of TLR TLR Postprocedural main vessel Reference diameter Odds ratio (95% C.I.) 0.48 ( ) P Value Severe calcification Total stent length Gender (Male) Hemodialysis DM 1.54 ( ) 1.02 ( ) 1.44 ( ) 1.61 ( ) 1.23 ( ) The j-cypher Registry

33 One stenting N=1889 (84.0%) Unknown:18 %DS> 50% N=1053(56.3%) SB %DS after MB stenting %DS<50% N=818(43.7%) FKB (+) N=562 (53.4%) FKB (-) N=491 (46.6%) FKB (+) N=376 (46.0%) FKB (-) N=442 (54.0%)

34 Role of FKB in Lesions <50% Side-branch Stenosis after Main-branch Stenting TLR (%) (%) Cumulative survival-free of TLR FKB (-) FKB (-) P=n.s Cumulative survival-free of ST Definite ST FKB (-) FKB (-) P=n.s Days after stent implantation Days after stent implantation No significant differences regarding TLR between FKB group and non-fkb group.

35 Role of KBT in Lesions 50% Side-branch Stenosis After Main-branch Stenting (%) 0.3 (%) Cumulative survival-free of TLR TLR FKB (-) FKB (-) P=n.s Days after stent implantation Cumulative survival-free of ST Definite ST FKB (-) FKB (-) P=n.s Days after stent implantation Even if the side branch %diameter stenosis was more than 50% after main branch stenting, the FKB did not provide the benefit regarding TLR.

36 Summary 1. The incidence of stent thrombosis in Asian races is relatively low. SAT LAST VLAST : 0.5% DES : 0.2% DES : 0.4%/2y DES 0.6% BMS 0.14% BMS 0 BMS at mean follow-up 5 years 2. Emergent procedure for AMI was an only predictor of ST in early ST and Hemodialysis, chronic renal failure(e-gfr < 30/Non-HD) and usage of two stent in bifurcation were predictor of late and very late ST. 3. Discontinuation of both thienopyridine and aspirin, but not discontinuation of thienopyridine therapy alone, was associated with an increased risk of Stent Thrombosis. 4. Landmark analysis did not suggest an apparent clinical benefit of thienopyridine use beyond 6 months after SES implantation

37 Summary Left Main Substudy from the j-cypher Registry 1. The adjusted survival rate was comparable between the Non LMT stenting group and LMT stenting group of patients. 2. Patients with ostial /body LMCA lesion had extremely low rate of TLR. 3. Among patients treated for ULMCA, bifurcation two stenting was associated with markedly higher rate of TLR and significantly higher rate of cardiac death.

38 Summary Left Main Substudy from the j-cypher Registry 1. The adjusted survival rate was comparable between the Non LMT stenting group and LMT stenting group of patients. 2. Patients with ostial /body LMCA lesion had extremely low rate of TLR. 3. Among patients treated for ULMCA, bifurcation two stenting was associated with markedly higher rate of TLR and significantly higher rate of cardiac death.

39 Bifurcation Substudy from the j-cypher Registry Summary Predictor of Target Lesion Revascularization in Elective Two-Stent Technique 1. True bifurcatiion lesion was seen in 64% of J-cypher: bifurcation. And among them, Elective two-stent strategy was used in 12.1% of all bifurcation lesions. 2. The incidence of death are 9.2% and TLR and definite stent thrombosis were 18.5 and 1.7%. 3. Total stent length, postprocedual main and side vessel diameter, two stent in circumflex and crush stenting were the predictor of TLR. The j-cypher Registry

40 Bifurcation Substudy from the j-cypher Registry Summary Role of Final Kissing Balloon Technique in Single Main Branch Stenting 1. The incidence of cardiac death, TLR and definite stent thrombosis were 3.5%, 9.5% and 0.72% at 3 year. 2. post main vessel diameter, severe calcification,total stent length, gender(male), Hemodialysis and DM were the predictor of TLR. 3. There was no significant differences regarding TLR between FKB group and non-fkb group. (Even if the side branch %diameter stenosis was more than 50% after main branch stenting, the FKB did not provide the benefit regarding TLR.) The j-cypher Registry

41 Twenty years ago

42 Shunsuke Koki Mizuno Nakamura Celtic/Scotland Espanyol/Spain Takahito Soma Maritimo/Portugal Daisuke Matsui Grenoble/France Takayuki Morimo Catania/Italy Shinji Ono Bochum/Germany Junichi Inamot Makoto Hasebe Stade Rennais/FranceWolfsburg/Germany

43 Let s Join Bifurcation Club EBC and JBC