Main Arena IV - Plenary Session XXVII: First Reports #4 I-LOVE-IT 2: A Prospective, Randomized Trial of a Biodegradable Polymer, Cobalt Chromium, Sirolimus-Eluting Stent Versus a Durable Polymer, Cobalt Chromium, Sirolimus-Eluting Stent in Patients with Coronary Artery Disease Bo Xu, MD On behalf of the I-LOVE-IT 2 Trial Investigators Fu Wai Hospital, National Center for Cardiovascular Diseases Beijing, China 12:00 PM-12:10 PM, Tuesday, September 16th, 2014 Washington DC, USA

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Financial Disclosures The study was sponsored by Essen Technology (Beijing, China), and was also supported by National Key Technology R&D Program in the 12th Five-Year Plan of China (2011BAI11B07) and Key Project of National 12th Five-Year Research Program of China (2012ZX093016 - 002) All of the authors have no relevant personal conflicts of interest to disclose Author Institute/Hospital Yaling Han, MD Bo Xu, MD Quanmin Jing, MD Shuzheng Lu, MD Lixia Yang, MD Kai Xu, MD Yi Li, MD Jing Li, MD Changdong Guan, MSc Ajay J. Kirtane, MD, SM Yuejin Yang, MD General Hospital of Shenyang Military Region, Shenyang, China Fu Wai Hospital, National Center for Cardiovascular Diseases, Beijing, China Affiliated Anzhen Hospital of Capital Medical University, Beijing, China General Hospital of Chengdu Military Region, Kunming, China Columbia University Medical Center / New York Presbyterian Hospital, New York, NY

Background No randomized trials have compared safety and efficacy of biodegradable polymer-coated sirolimus-eluting stent (BP-SES) versus durable polymer-coated sirolimus-eluting stent (DP-SES) on similar cobalt-chromium platforms, thereby isolating the effect of the polymer type Moreover, optimal duration of dual antiplatelet therapy (DAPT) after BP-SES implantation remains underdetermined Stefanini GG, et al, Eur Heart J 2012 Christiansen EH, et al, Lancet 2013

Study Design and Patient Flow Real-world patients eligible for coronary stenting were randomized in a 2:1 ratio 6-month DAPT for BP-SES n=909 BP-SES n=1829 DP-SES n=908 ® 12-month DAPT for BP-SES n=920 6 months 9 months 1 year Clinical Endpoints 30 days 2 years 3 years 4 years 5 years Primary Endpoint: 1-year TLF (composite of cardiac death, TVMI, and CI-TLR) Major Secondary Endpoints: 1-year TLF and NACCE (composite of death, MI, stroke, major bleeding (BARC >= II)) between 6- and 12-month DAPT groups after BP-SES implantations Secondary Endpoints: individual TLF components, definite/probable stent thrombosis, device/lesion/procedure success rates, and PoCE (composite of all cause death, all MI, and any revascularization) *TLF = target lesion failure; TVMI = target vessel myocardial infarction; CI-TLR = clinically indicated target lesion revascularization; NACCE = net adverse clinical and cerebral events; PoCE = patient-oriented composite endpoint

Primary Endpoint: TLF at 1 Year (Cardiac Death, TVMI, and CI-TLR) BP-SES (n = 1818) 6.3% DP-SES (n = 905) 6.1% Difference : 0.25% Upper 1-sided 95% CI: 2.17% Noninferiority P value = 0.0002 Zone of noninferiority Pre-specified margin = 3.7% Non-inferior % 0.5 1.0 4.0 2.5 3.0 3.5 -0.5 1.5 2.0 Upper one-sided 95% CI Primary Noninferiority Endpoint Met

TLF and Components at 1 Year Cumulative Event Rates (%) P = 0.80 P = 0.39 P = 0.50 P = 0.62 115/ 1818 55/ 905 66/ 39/ 48/ 20/ 13/ 5/

Def/Prob Stent Thrombosis at 1 Year Cumulative Incidence of Events (%) Acute ST (0-1 day) n=3 Subacute ST (2-30 days) n=3 Late ST (31-365 days) n=1 Acute ST (0-1 day) n=2 Subacute ST (2-30 days) n=2 Late ST (31-365 days) n=1 Cumulative Incidence of Events (%) P = 0.55 0.6% (n=5) 0.4% (n=7)

Conclusions The present I-LOVE-IT 2 trial has demonstrated that the BP-SES is non-inferior in terms of efficacy to DP-SES in clinical practice. Whether BP-SES improves safety with respect to lowering stent thrombosis incidence compared with DP-SES, remains to be shown in longer-term follow-up of this trial or in future studies.

Backup Slides

Comparison of Specifications between BP-SES and DP-SES Manufactory Essen Technology, Beijing, China MicroPort, Shanghai, China Stent Platform Material Cobalt-Chromium (L605) Strut Thickness 0.080 mm 0.086 mm Stent Profile < 1.10 mm < 1.12 mm Diameter 2.50, 2.75, 3.00, 3.50, 4.00 mm Length 10, 15, 18, 21, 25, 30, 35 mm 13, 18, 23, 29, 33 mm Drug Sirolimus Drug Dose 8 μg/mm 9 μg/mm Polymer PLGA (biodegradable) SBS (durable) Polymer Thickness 5.5 µm 6.0 µm Drug Release 75% at 28 days > 80% at 30 days Tivoli® Firebird 2TM

Target Lesion Failure Through 1 Year Cumulative Incidence of Events (%) Time since Index Procedure (Days) 360 300 240 180 120 60 10 8 6 4 2 BP-SES DP-SES Log-rank P = 0.97 6.3% 6.1% Patients at Risk: Days 60 120 180 240 300 360 BP-SES 1829 1766 1760 1754 1735 1724 1708 DP-SES 908 864 860 859 856 854 849

Clinical Outcomes at 1 Year BP-SES (n=1818) DP-SES (n=905) P Target Lesion Failure 6.3 (115) 6.1 (55) 0.80 All Cause Death 1.4 (25) 1.0 (9) 0.40 Cardiac Death 0.7 (13) 0.6 (5) 0.62 All Myocardial Infarction 4.2 (77) 4.6 (42) 0.63 Q-wave Myocardial Infarction 0.8 (14) 0.9 (8) 0.75 Non-Q-wave Myocardial Infarction 3.5 (64) 3.8 (34) Target Vessel Myocardial Infarction 3.6 (66) 4.3 (39) 0.39 Any Revascularization 5.1 (92) 4.9 (44) 0.82 Target Vessel Revascularization 3.2 (58) 2.8 (25) 0.54 Target Lesion Revascularization 2.6 (48) 2.3 (21) Clinically Indicated Target Lesion Revascularization 2.2 (20) 0.50 All Cause Death, All MI, and Any Revascularization 9.7 (176) 9.4 (85) 0.81 Definite/Probable Stent Thrombosis 0.4 (7) 0.55 Definite Stent Thrombosis 0.2 (3) 0.4 (4) 0.23 Probable Stent Thrombosis 0.2 (4) 0.1 (1) 1.00 Acute (0-1 day) 0.2 (2) 0.67 Subacute (2-30 days) Late (31-365 days)

TLF Among Subgroups at 1 Year p Value for Interaction Target Lesion Failure - Events/Total (%) Relative Risk (95% CI) p Value for Interaction BP-SES DP-SES p Value Age <65 years ≥65 years 73/1242 (5.9) 42/587 (7.2) 36/618 (5.8) 19/290 (6.6) 0.96 0.74 1.01 (0.68-1.49) 1.09 (0.65-1.84) 0.81 Gender Male Female 69/1243 (5.6) 46/586 (7.8) 41/636 (6.4) 14/272 (5.1) 0.43 0.15 0.86 (0.59-1.25) 1.53 (0.85-2.73) 0.10 Body mass index <30 ≥30 108/1682 (6.4) 5/114 (4.4) 51/828 (6.2) 4/65 (6.2) 0.80 0.73 1.04 (0.76-1.44) 0.71 (0.20-2.56) 0.57 Diabetes mellitus Yes No 38/414 (9.2) 77/1415 (5.4) 14/193 (7.3) 41/715 (5.7) 0.78 1.27 (0.70-2.28) 0.95 (0.66-1.37) 0.42 Current smoker 36/685 (5.3) 79/1144 (6.9) 22/335 (6.6) 33/573 (5.8) 0.40 0.36 0.80 (0.48-1.34) 1.20 (0.81-1.78) 0.22 Emergent PCI for AMI 11/86 (12.8) 104/1743 (6.0) 8/51 (15.7) 47/857 (5.5) 0.64 0.62 0.82 (0.35-1.89) 1.09 (0.78-1.52) 0.53 Multivessel PCI 37/473 (7.8) 78/1356 (5.8) 19/252 (7.5) 36/656 (5.5) 0.89 0.82 1.04 (0.61-1.77) 1.05 (0.71-1.54) 0.98 Number of treated lesion 1 ≥2 72/1257 (5.7) 43/572 (7.5) 33/623 (5.3) 22/285 (7.7) 0.70 0.92 1.08 (0.72-1.61) 0.97 (0.59-1.60) 0.75 Preprocedural TIMI flow 0-2 3 36/452 (8.0) 79/1377 (5.7) 21/213 (9.9) 34/694 (4.9) 0.81 (0.48-1.35) 1.17 (0.79-1.73) Chronic total occlusion 24/294 (8.2) 91/1535 (5.9) 14/148 (9.5) 41/759 (5.4) 0.65 0.61 0.86 (0.46-1.62) 1.10 (0.77-1.57) Bifurcation 47/717 (6.6) 45/765 (5.9) 29/362 (8.0) 26/545 (4.8) 0.38 0.27 0.82 (0.52-1.28) 1.28 (0.83-1.99) Reference vessel diameter ≤2.75 mm >2.75 mm 70/1064 (6.6) 30/483 (6.2) 25/424 (5.9) 0.79 0.99 1.06 (0.70-1.60) 1.00 (0.62-1.60 0.85 Lesion length ≤20 mm >20 mm 38/939 (4.0) 77/890 (8.7) 25/459 (5.4) 30/448 (6.7) 0.24 0.21 0.74 (0.45-1.22) 1.29 (0.86-1.94) 0.09 Overall 115/1829 (6.3) 55/908 (6.1) 1.04 (0.76-1.42)