PROMUS Element Experience In AMC

Promus Element Luncheon Symposium: PROMUS Element Experience In AMC Jung-Min Ahn, MD. University of Ulsan College of Medicine, Heart Institute, Asan Medical Center, Seoul, Korea

PROMUS Element Clinical Programs In Asan Medical Center Left Main Disease Long Lesion ( 28mm) Real World Registry Historical Comparison of RCT of Registry of PROMUS Element Everolimus-Eluting Stent PROMUS Element Everolimus-Eluting Stent PROMUS Element Everolimus-Eluting Stent Promary Endpoint Compared to Promary Endpoint Composite of Death MI Stroke Ischemic driven TVR At 12-months Nobori Biolimus-Eluting Stent Promary Endpoint 9 Months In-segment LL Composite of Death MI TVR at 12-months

Comparison of Platinum Chromium Versus Cobalt Chromium Everolimus-Eluting Stent in Real World Practice: Outcomes from the Multicenter Prospective IRIS-DES Registry

Comparison of PtCr-EES and CoCr-EES from IRIS-DES Registry Consecutive PCI patients receiving New DES without a mixture of other DES Prospective Enrollment since 2007 in Korean multicenters DESSIAN Registry 2008.4-2010.5 K-XIENCE Registry 2010.1-2011.12 IRIS- ELEMENT Registry IRIS- NOBORI Registry IRIS- BIOMATRIX Registry IRIS- GENOUS Registry IRIS- PRIME Registry IRIS- RESOLUTE Registry IRIS- CILOTAX Registry CYPHER (N=3,600) XIENCE (N=3,000) PROMUS ELEMENT (N=3,000) NOBORI (N=2,000) BIOMATRIX (N=1,000) GENOUS STEMI (N=1,000) XIENCE-PRIME (N=2,000) RESOLUTE INTEGRITY (N=1,000) CILOTAX (N=1,000) Clinical follow-up at 1-, 6-, and 12-months, and annually up to 5 years

Study Population Inclusion Criteria All consecutive patients who have 1 coronary lesion with a visual estimated DS of >50%. Revascularization was clinically indicated Exclusion Criteria Cardiogenic shock A contraindication to the placement of DESs life expectancy <12 months. PCI with a mixture of different types of DES

Study Endpoints Primary Endpoint Death Myocardial Infarction Target vessel revascularization Secondary End Point Cardiac and non-cardiac deaths. Periprocedural MI (Q wave MI or CK-MB>3UNL) Spontaneous MI (cardiac enzyme elevation). Repeat revascularization: TVR, TLR, & NLR Stent thrombosis: ARC definite or probable ST Stent length and number implanted

Baseline Characteristics PtCr-EES (N=2990) CoCr-EES (N=3081) P value Age 63.8±10.9 63.5±10.8 0.21 Sex, Male 2113 (70.7%) 2079 (67.5%) 0.007 DM 1013 (33.9%) 1026 (33.3%) 0.63 Hypertension 1827 (61.1%) 1922 (62.4%) 0.31 Hyperlipidemia 1088 (36.4%) 1155 (37.5%) 0.38 Smoking 872 (29.2%) 891 (28.9%) 0.83 Previous PCI 319 (10.7%) 454 (14.7%) <0.001 Previous CABG 36 (1.2%) 62 (2.0%) 0.012 Previous MI 150 (5.0%) 159 (5.2%) 0.80 Previous CHF 81 (2.7%) 67 (2.2%) 0.18

Baseline Characteristics PtCr-EES (N=2990) CoCr-EES (N=3081) P value Family History 200 (6.7%) 111 (3.6%) <0.001 Chronic renal failure 95 (3.2%) 105 (3.4%) 0.62 Previous stroke 215 (7.2%) 252 (8.2%) 0.15 Peripheral vascular disease 62 (2.1%) 36 (1.2%) 0.005 Chronic lung disease 61 (2.0%) 92 (3.0%) 0.019 Ejection fraction, % 59.1±10.1 59.5±10.9 0.19 Presentation <0.001 Stable angina 1143 (38.2%) 1277 (41.4%) Unstable angina 1008 (33.7%) 1057 (34.3%) NSTEMI 480 (16.1%) 339 (11.0%) STEMI 359 (12.0%) 408 (13.2%)

Lesion and Procedure Characteristics PtCr-EES (N=2990) CoCr-EES (N=3081) P value Multivessel disease 1470 (49.2%) 1636 (53.1%) 0.002 LMCA disease 213 (7.1%) 323 (10.5%) <0.001 LAD disease 2189 (73.2%) 2336 (75.8%) 0.02 Bifurcation lesion 903 (30.3%) 819 (34.0%) 0.004 Total obstruction 648 (21.7%) 359 (14.7%) <0.001 Restenotic lesion 115 (3.8%) 179 (5.8%) <0.001 Long lesion 1693 (56.7%) 1882 (61.1%) <0.001 Multivessel stenting 772 (35.4) 563 (25.8) <0.001 Total treated lesion number 1.33±0.61 1.37±0.64 0.004 Total stent number 1.620.90 1.82±1.16 <0.001 Total stent length 36.9±23.2 41.7±30.0 <0.001 Average stent diameter, mm 3.17±0.44 3.22±0.44 <0.001

1 - 누적생존함수 Cumulative Incidence, % 0.3 30 Group Unadjusted Kaplan-Meier Curve 2 3 0.4 2-중도절단됨 Primary End Point (Death, MI, or Target Vessel Revascularization) 3- 중도절단됨 PtCr -EES CoCr-EES 0.2 20 Log-Rank P=0.12 0.1 10 15% 15% No. at Risk PtCr-EES CoCr-EES 0.0 0 0 120 240 360 480 600 720 0 120 240 360 480 600 720 Days Since Procedure 2990 3081 2578 2720 DMITVR_du 900 2503 450 2251

1 - 누적생존함수 Cumulative Incidence, % 0.5 Adjusted Kaplan-Meier Curve Group 2 3 0.4 Primary End Point (Death, MI, or Target Vessel Revascularization) 0.3 30 PtCr -EES CoCr-EES 0.20 HR (95%CI) 1.01 (0.87-1.18), P=0.89 0.110 No. at Risk PtCr-EES CoCr-EES 0.0 0 0 120 240 360 480 600 720 0 120 240 360 480 600 720 Days Since Procedure 2990 3081 2578 2720 DMITVR_du 900 2503 450 2251

Cumulative Incidence, % 1 - 누적생존함수 0.5 Adjusted Kaplan-Meier Curve 3 0.4 0.3 30 5 Death HR (95%CI) 1.27 (0.91-1.772), p=0.16 4 2-Year Event Rate PtCr -EES CoCr-EES 0.2 20 3 P=0.33 P=0.8 0.1 10 2 1 0 1 Cardiac Death 1.5 1.5 1.5 Non-CD No. at Risk PtCr-EES CoCr-EES 0.0 0 0 120 240 360 480 600 720 0 120 240 360 480 600 720 Days Since Procedure 2990 3081 2745 2986 fu_du 996 2827 499 2567

Cumulative Incidence, % 1 - 누적생존함수 0.5 Adjusted Kaplan-Meier Curve 0.4 0.3 30 0.2 20 0.1 10 Myocardial Infarction 14 12 10 8 HR (95%CI) 0.89 (0.71-1.11), P=0.27 6 2-Year Event Rate P<0.001 P=0.35 7.4 5 4 2 1.2 1.3 0 Peri-MI Spon-MI 2 3 PtCr -EES CoCr-EES No. at Risk PtCr-EES CoCr-EES 0.0 0 0 120 240 360 480 600 720 2990 3081 0 120 240 360 480 600 720 Days Since Procedure 2600 2761 anymi_du 940 2603 458 2362

1 - 누적생존함수 Cumulative Incidence, % Adjusted Kaplan-Meier Curve 0.4 0.330 1 - 생존함수 Death or MI Group 2 3 PtCr -EES CoCr-EES 0.220 HR (95%CI) 0.95 (0.79-1.13), P=0.54 0.1 10 No. at Risk PtCr-EES CoCr-EES 0.0 0 0 120 240 360 480 600 720 0 120 240 360 480 600 720 Days Since Procedure 2990 3081 2578 2720 DMI_du 900 2525 449 2229

1 - 누적생존함수 Cumulative Incidence, % Adjusted Kaplan-Meier Curve 0.3 0.2 30 20 16 14 12 10 8 6 4 P=0.30 TVR 1 - 생존함수 2-Year Event Rate P=0.51 HR (95%CI) 1.13 (0.86-1.50), P=0.39 9.1 7.4 4.1 4.3 3.9 P=0.14 5.3 PtCr -EES CoCr-EES Group 2 3 0.1 10 2 0 Any TLR NLR No. at Risk PtCr-EES CoCr-EES 0.0 0 0 120 240 360 480 600 720 0 120 240 360 480 600 720 TVR_du Days Since Procedure 2990 3081 2719 2931 956 2701 477 2439

% Stent Thrombosis at 24 Months* 1.0 0.8 P=0.33 0.6 0.4 15 (0.5) 7 (0.4) 0.2 0.0 PtCr-EES (N=2990) CoCr-EES (N=3081) * ARC defined definite and probable stent thrombosis

Percutaneous Treatment of LONG Native Coronary Lesions with Drug-Eluting Stent-V: Biolimus A9-Eluting (NOBORI) vs. Everolimuseluting (PROMUS-ELEMENT) Stent A Randomized LONG-DES V Trial

Design Patients requiring PCI with DES for long coronary lesions: Lesion length 25mm (total stent length 28mm) R Biolimus A9-eluting stent: Nobori (n=250) Everolimus-eluting stent: Promus-Element (n=250) 9 months Angiographic follow-up 12 months Clinical follow-up Primary endpoint: In-segment late loss at 9 months angiographic follow-up ClinicalTrials.gov Identifier: NCT01186120

Inclusion Criteria Clinical Criteria Patients with sap, ACS or inducible ischemia At least 18 years old Angiographic Criteria De novo long coronary lesion suitable for stenting Diameter stenosis >50% by visual estimation Reference vessel size 2.5 mm by visual estimation Lesion length 25 mm by visual estimation (planned total stent length 28mm)

Baseline Characteristics NOBORI (N=245) P-Element (N=255 ) P Value Age 63.06±10.46 63.49±10.63 0.65 Male sex 167 (68.2) 184 (72.2) 0.38 Diabetes mellitus 79 (32.2) 89 (34.9) 0.33 Hypertension 161 (65.7) 154 (60.4) 0.23 Hyperlipidemia 131 (53.5) 145 (56.9) 0.36 Current smoker 63 (25.7) 74 (29.0) 0.42 Previous coronary angioplasty 16 (6.5) 26 (10.2) 0.15 Previous myocardial infarction 6 (2.4) 11 (4.3) 0.32 Left ventricular ejection fraction, % 60.29±7.56 60.23±7.48 0.93

Baseline Characteristics NOBORI (N=245) P-Element (N=255 ) P Value Clinical indication 0.80 Silent ischemia 22 (9.0) 17 (6.7) Stable angina 120 (49.0) 128 (50.2) Unstable angina 68 (27.8) 74 (29.0) Myocardial infarction 35 (14.3) 36 (14.1) Number of Diseased Vessel 0.34 1-vessel 121 (49.4) 115 (45.1) 2-vessel 76 (31.0) 95 (37.3) 3-vessel 48 (19.6) 45 (17.6) multi-vessel disease 124 (50.6) 140 (54.9) 0.37

Lesion Characteristics NOBORI (N=245) P-Element (N=255 ) P Value Target vessel 0.72 Left anterior descending 159 (64.9) 171 (67.1) Left circumflex 33 (13.5) 32 (12.5) Right coronary 53 (21.6) 52 (20.4) TIMI flow grade=0 or 1 25 (10.2) 21 (8.2) 0.46 Bifurcation lesions 79 (32.2) 63 (24.7) 0.04 Thrombus 11 (4.5) 8 (3.1) 0.48 Severe tortuosity 3 (1.2) 4 (1.6) 0.93 Severe Calcification 26 (10.6) 32 (12.5) 0.10 Ulceration 16 (6.5) 16 (6.2) 0.95

Procedural Characteristics NOBORI (N=245) P-Element (N=255 ) P Value No. of stents used at the target lesion 0.20 1 stent 115 (46.9) 117 (45.9) 2 stents 116 (47.3) 110 (43.1) 3 stents 13 (5.3) 26 (10.2) 4 stents 1 (0.4) 2 (0.8) mean 1.59±0.61 1.65±0.69 0.25

Procedural Characteristics Nobori (N=245) P-Element (N=255 ) P Value Stented Length at target, mm 36.06±11.48 39.32±13.82 0.005 Average stent diameter, mm 3.16±0.29 3.18±0.37 0.41 Maximal pressure, atm 12.05±4.01 13.51±3.51 <0.001 Direct stenting 16 (6.5) 12 (4.7) 0.44 Post-additional balloon inflation 190 (77.6) 178 (69.8) 0.06 Intravascular ultrasound guidance 189 (77.1) 188 (73.7) 0.41 Glycoprotein IIb/IIIa antagonists 5 (2.0) 6 (2.4) 0.99

QCA Before Procedure NOBORI (N=245) P-Element (N=255 ) P Value Lesion length, mm 29.24±12.17 32.27±13.84 0.016 Reference vessel diameter, mm 3.02±0.46 3.03±0.45 0.80 Minimal luminal diameter, mm 0.85±0.42 0.83±0.42 0.41 Diameter stenosis, % 71.71±13.38 72.61±13.95 0.48

QCA After Procedure Minimal luminal diameter, mm NOBORI (N=245) P-Element (N=255 ) P Value In segment 2.23±0.43 2.21±0.40 0.52 In stent 2.52±0.40 2.52±0.36 0.49 Proximal margin 3.01±0.56 3.07±0.52 0.33 Distal margin 2.26±0.45 2.24±0.43 0.48 Diameter stenosis, % In segment 17.80±9.97 17.12±10.0 0.46 In stent 10.62±8.77 9.99±8.27 0.36 Proximal margin 12.28±9.18 11.15±9.14 0.20 Distal margin 15.18±9.73 14.90±10.20 0.76 Acute gain, mm In segment 1.36±0.53 1.38±0.61 0.88 In stent 1.67±0.51 1.68±0.57 0.86

Study Endpoint Primary Endpoint In-segment late luminal loss At 9 months after the index procedure

Follow-up Analysis Nobori N=245 Promus Element N=255 95 pts refused follow-up 2 pts died 107 pts refused follow-up 1 pts died 9-month angiographic follow-up N=148 (60%) 9-month angiographic follow-up N=147 (58%) 12-month clinical follow-up N=250 (100%) 12-month clinical follow-up N=250 (100%)

QCA at Follow-up NOBORI (N=148) P-Element (N=147) P Value Minimal luminal diameter, mm In segment 2.09±0.47 2.08±0.49 0.86 In stent 2.39±0.48 2.22±0.45 0.009 Proximal margin 2.89±0.60 2.82±0.60 0.33 Distal margin 2.15±0.44 2.22±0.45 0.27 Diameter stenosis, % In segment 21.0±15.4 24.1±14.2 0.10 In stent 14.9±14.1 21.6±15.5 <0.001 Proximal margin 15.5±12.0 16.6±12.4 0.50 Distal margin 17.2±12.8 14.6±9.7 0.07

Primary Endpoint: In-Segment Late Loss at 9 months Nobori : 0.11±0.40 mm P-Element : 0.12±0.39 mm

MACE (death/mi/tvr) at 12 months

Summary In the large, multi-center, prospective cohort study involving real-world patients undergoing PCI with DES, PtCr-EES sh owed the similar clinical efficacy and safety with CoCr-EES. In addition, In the prospective, randomized trial involving patients with long coronary artery lesions, PtCr-EES and BES showed similar 9 month angiographic in-segment late luminal loss.