3-Year Clinical Outcomes From the RESOLUTE US Study Paul Teirstein, MD On behalf of the RESOLUTE US Investigators ACC.13

Author Disclosure Research grants, speaker fees and consulting with Medtronic, Inc. Boston Scientific Corporation and Abbott

Abstract – 3-Year Follow-up of the RESOLUTE US Clinical Trial Background: Long-term follow-up of patients treated with new generation drug-eluting stents contributes to our understanding of the risks and benefits of these devices over time. RESOLUTE US was a prospective single-arm trial designed to evaluate the effectiveness of the Resolute™ zotarolimus- eluting stent (R-ZES) in patients with de novo coronary artery disease. Methods: Patients with lesions in vessels 2.25–4.0 mm in diameter and appropriate for one- or two-vessel treatment were enrolled. The primary endpoint at 1 year was target lesion failure (TLF); a composite of cardiac death, target vessel myocardial infarction (TVMI), and target lesion revascularization (TLR). Secondary endpoints include the components of TLF and definite/probable stent thrombosis (ST). Dual antiplatelet therapy (DAPT) was prescribed for a minimum of 6 months. Annual follow-up was obtained through 5 years. Results: There were 1402 patients enrolled; 68.3% males and 34.4% with diabetes, including 9.6% using insulin. Most lesions were type B2/C (75%). TLF at 2 years was 7.3% including 4.3% TLR, 1.9% TVMI and 1.5% cardiac death. Overall definite/probable ST occurred in 3 (0.2%) and1 patients (0.1%) between 1 and 2 years respectively; 67.2% of patients were on DAPT at 2 years. There were 150 patients with vessels <2.25 mm and among this cohort the 2-year rate of TLF was 8.2%. Two of the 3 ST events occurred in this cohort. Among patients with diabetes the 2-year rate of TLF was 8.9% and TLR was 5.7%. There was no ST in the diabetic subgroup through 2 years. Conclusions: Two-year follow-up demonstrates low rates of TLF in all patient cohorts with very low rates of ST following treatment of coronary artery disease with the R-ZES. Outcomes in patients with diabetes further support the safety and effectiveness of the R-ZES. Full 3-year follow-up of the RESOLUTE US trial will be presented at ACC2013.

RESOLUTE Global Clinical Program Enrollment Complete – In Follow-up RESOLUTE1 Non-RCT First-in-Human (R = 139) 5 yr RESOLUTE AC2,3 1:1 RCT vs Xience V (R = 1140; X = 1152) 3 yr RESOLUTE Int4 Non-RCT Observational (R = 2349) 3 yr RESOLUTE US5 2.25–4.0 mm Non-RCT vs Hx Control (R = 1402) 3 yr RESOLUTE Japan 2.5–3.5 mm Non-RCT (R = 100) vs Hx Control 2 yr R Japan SVS 2.25 Non-RCT vs PG (R = 65) 1 yr RESOLUTE US 38 mm Substudy Non-RCT vs PG (R = 114) 1 yr R-China RCT 1:1 RCT vs Taxus (R = 200; T = 200) 1 yr RESOLUTE Asia Non-RCT Observational (R = 312) 1 yr R-China Registry Non-RCT Observational (R = 1800) 1 yr Enrolling / Planning RI-US Registry Post-approval Study (R ≈ 230) Enrolling 1Meredith IT, et al. EuroIntervention. 2010;5:692-7. 2Serruys PW, et al. N Engl J Med. 2010;363:136-46. 3Silber S, et al. Lancet. 2011;377:1241-47. 4Neumann FJ, et al. EuroIntervention. 2012;7(10):1181-8. 5Yeung AC, et al. JACC. 2011;57:1778-83. 4

De Novo Native Coronary Lesion (≤35 mm lesions tx w/ 38 mm stent) RESOLUTE US Clinical Study Design De Novo Native Coronary Lesion Vessel Diameter: 2.25–4.2 mm Lesion Length: ≤27 mm (≤35 mm lesions tx w/ 38 mm stent) Resolute™ stent 2.25–3.5 Clinical (n = 1242) 2.25–3.5 Angio/IVUS (n = 100) 4.0 Angio (n = 60) 38 mm Clinical (n = 110–175) Hx Controls Performance Goals N = max 1577 patients Up to 135 US sites Clinical endpoints 30d 6mo 8mo 9mo 12mo 18mo 2yr 3yr 4yr 5yr Angio/IVUS endpoints Primary Endpoints: 2.25–3.5 Clinical → Target Lesion Failure at 12 mo 2.25–3.5 Angio/IVUS → In-Stent LLL at 8 mo 4.0 Angio → In-Segment LLL at 8 mo 38 mm Clinical → Target Lesion Failure at 12 mo Drug Therapy: ASA and clopidogrel/ticlopidine ≥6 mo (per guidelines)

Key Inclusion Criteria Key Exclusion Criteria RESOLUTE US Key Eligibility Criteria Key Inclusion Criteria Clinical evidence of ischemic coronary disease Single or double de novo lesion in native coronary artery Target lesion ≤27 mm in length, diameter stenosis ≥50% <100%, and target RVD ≥2.25 mm ≤4.2 mm Target vessel TIMI flow ≥2 Patient is able to take DAPT for at least 6 months Treatment of up to two lesions, if the lesions are located in separate target vessels Key Exclusion Criteria Acute MI within 72 hours of index procedure Previous PCI of target vessel within 9 months pre-procedure Planned PCI of any vessel within 30 days post-procedure Hx stroke or TIA within 6 months LVEF <30% Mauri L, et al. Am Heart J. 2011;161:807-14.

RESOLUTE US Patient Flow Chart Patients Enrolled N = 1402 1-Year Clinical Follow-up n = 1386 98.9% 2-Year Clinical Follow-up n = 1359 96.9% 3-Year Clinical Follow-up n = 1341 95.6% 7 7

RESOLUTE US Baseline Characteristics % All Patients (2.25 mm–4.00 mm diameter) N = 1402 Patients / 1573 Lesions Age, years (mean ± SD) 64.1 ± 10.7 Male 68.3 Diabetes mellitus 34.4 IDDM 9.6 Prior PCI 32.7 Reason for revascularization: Stable angina 56.1 Unstable angina 41.9 Myocardial infarction 2.1 LAD 45.9 RVD (mm) 2.6 ± 0.5 Type B2/C lesion 75.2 Two vessel treatment 10.4 Stents per patient (mean ± SD) 1.2 ± 0.5 Stent length per patient (mm) 22.4 ± 10.5 Yeung AC, et al. J Am Coll Cardiol. 2011;57:1778-83.

RESOLUTE US Primary Endpoint and Substudy Analyses Primary Endpoint Analysis: Target Lesion Failure Resolute™ ZES (2.5–3.5 mm) N = 1001 3.7% Difference: -2.8% Upper 1-sided 95% CI: -1.3% Non-inferiority P-value <0.001 Hx Control (E-ZES) N = 1092 6.5% Primary Non-Inferiority Met Post-Hoc Superiority Met Psup = 0.002 Substudy Endpoints 2.25 mm Stent Group N = 150 patients N = 197 lesions TLF at 12 months cw PG: 20% 4.8% Upper 1-sided 95% CI: 8.8% PG: 20% Primary Endpoint Met P <0.001 Angiographic Cohorts In-stent late lumen loss at 8 mos for 2.25 – 3.5 vessels cw Endeavor™ ZES Historical control (non-inferiority) Resolute™ ZES N = 100 0.39 ± 0.06 Historical Control Endeavor 0.61 ± 0.03 Difference: -0.22 Upper 1-sided 95% CI: -0.11 Non-inferiority Endpoint Met In-segment late lumen loss at 8 mos for 4.0 vessels cw BMS Historical control (superiority) N = 60 0.11 ± 0.09 Historical Control Driver N = 150) 0.66 ± 0.05 Difference: -0.56 Upper 1-sided 95% CI: -0.38 Superiority Endpoint Met

RESOLUTE US – All Patients Target Lesion Failure to 36 Months 15% RUS 10% Cumulative Incidence of TLF 5% 0% 360 720 1080 Time After Initial Procedure (days) RUS No. at risk 1402 1384 1301 1217 % CI 1.28 4.68 7.28 8.38

RESOLUTE US – All Patients Clinical Outcomes at 12 and 36 Months % 12 Months* n = 1386 36 Months n = 1341 Death (all) 1.3 4.7 Cardiac 0.6 2.1 MI (target vessel) Q Wave 0.1 Non Q wave 1.2 1.9 Cardiac death + target vessel MI 3.9 ST Def/Prob (all) 0.3 Early (0-30 days) Late (31-360 days) Very late (>360 days) – TLR 2.8 4.9 TVR 4.5 9.7 TLF (cardiac death, TVMI, TLR) 4.6 8.5 TVF 6.1 12.7 * M. Leon ACC 2011.

RESOLUTE US – All Patients Safety and Efficacy Outcomes at 36 Months Resolute™ ZES (n = 1341/1402) Events (%) 114/1341 66/1341 28/1341 28/1341 4/1341 Target lesion failure (TLF) is defined as cardiac death, target vessel MI and clinically-driven TLR. TLR is ischemia driven.

Time After Initial Procedure (days) RESOLUTE US DAPT to 36 Months RUS (N = 1402) 95.7 97.2 93.7 73.5 66.3 Adherence to DAPT (%) 56.9 Time After Initial Procedure (days)

RESOLUTE US Def/Prob Stent Thrombosis to 36 Months RUS 5% 4% 3% Cumulative Incidence of ARC Def/Prob Stent Thrombosis 2% 1% 0% 360 720 1080 Time After Initial Procedure (days) RUS No. at risk 1402 1354 1292 % CI 0.00 0.14 0.22 0.30

RESOLUTE US – All Patients Stent Thrombosis at 36 Months % (n) 30 Days n = 1399 1 Year n = 1386 2 Years n = 1359 3 Years n = 1341 Stent thrombosis (ARC def/prob) 0.1 (1) 0.1 (2) 0.2 (3) 0.3 (4) Early (<30 days) Late (31-360 days) n/a Very late (>360 days) 30 Days - The RESOLUTE US Trial – Yeung et al. JACC Vol. 57, No. 17, 2011. 1 and 2 Year - Tolleson – SCAI 2012.

RESOLUTE US Main Study (2.5–3.5 mm single lesion) Safety and Efficacy Outcomes at 36 Months Resolute™ ZES (n = 1064/1112) Events (%) 76/1064 43/1064 18/1064 21/1064 2/1064 Target lesion failure (TLF) is defined as cardiac death, target vessel MI and TLR (ischemia driven). TLF rate at 2 years for Endeavor ZES was 8.1% (post-hoc analysis, Pnoninferiority < 0.001).

RESOLUTE US – Diabetic Patients Safety and Efficacy Outcomes at 36 Months Resolute™ ZES (n = 465/482) Events (%) 50/465 31/465 14/465 7/465 0/465 Target lesion failure (TLF) is defined as cardiac death, target vessel MI and clinically-driven TLR. TLR is ischemia driven.

RESOLUTE US Conclusions Out to 3 years, the TLF (primary endpoint) was consistently low All patients 8.5%, main cohort (2.5-3.5 single lesion) 7.1% Stent thrombosis was very low (0.2%) with only 1 new ST event after 1 year Very good outcomes in the diabetic subgroup Low rate of TLF (10.8%) and TLR (6.7%) No stent thrombosis out to 3 years