Long Term Safety and Effectiveness of XIENCE V® Everolimus Eluting Coronary Stent System in a Real-World Population: Three-Year Clinical Outcomes from XIENCE V® USA James B. Hermiller, Jr,1 Weiying Zhao,2 Luis Gruberg,3 William Lombardi,4 David R. Rutledge,2 Jin Wang,2 and Vivian W. Mao,2 and Mitchell W. Krucoff5 The Heart Center of IN, Indianapolis, Indiana Abbott Vascular, Santa Clara, CA Stony Brook University, Stony Brook, NY Peacehealth St. Joseph Medical Center, Bellingham, WA Duke University Medical Center, Durham, NC 1

Disclosures James B. Hermiller: Abbott Vascular, Boston Scientific, Medtronic, and St. Jude: Consultant Fee/Honoraria/Speaker’s Bureau Mitchell W. Krucoff: Abbott Vascular, Biosensors International, Boston Scientific, Cordis, Medtronic, Terumo, St. Jude Medical, Angel Medical Systems, Edwards Lifesciences, Cappella: Research Grant; Abbott Vascular, Biosensors International, Boston Scientific, Cordis, Medtronic, Terumo, St. Jude Medical, Angel Medical Systems, Guided Delivery Systems, Edwards Lifesciences, Cardiac Dimensions Inc., Cappella: Research Consultant/Advisory Board and Speaker’s Bureau Luis Gruberg: Eli Lilly, Daiichi Sankyo, AstraZeneca, and The Medicines: Consultant Fee/Honoraria/Speaker’s Bureau William Lombardi: Abbott Vascular and Medtronic: Consultant Fee/Honoraria/Speaker’s Bureau ; Bridgepoint Medical Systems: Equity David R. Rutledge, Vivian W. Mao, Weiying Zhao, Jin Wang: Abbott Vascular employees. This study was sponsored by Abbott Vascular (Santa Clara, CA, USA). XIENCE V® USA

Introduction A recent 1-year multivariable analysis of real-world XVUSA patients demonstrated several independent predictors of adverse events. Early DAPT interruption (≤30 days) was the most potent predictor of ST, whereas delayed interruption (>30 days) was not predictive. XIENCE V® USA

Introduction The safety and effectiveness of XIENCE V in these real-world patients continue to demonstrate low stent thrombosis and cardiac death/MI rates at two years (J Interv Card 2012, in press). The objective of this analysis is to present 3-year results and to model for the first time multivariate predictors after 1 year. XIENCE V® USA

Methods XIENCE V USA is a large, prospective, multicenter, post-approval study designed to examine the safety and effectiveness of XIENCE V in patients from real-world clinical settings. Patients were consecutively enrolled with no inclusion/exclusion criteria beyond informed consent and the exclusive use of XIENCE V during the index procedure. The primary and co-primary endpoints were Academic Research Consortium (ARC)-defined ST (definite/probable) and the composite rate of cardiac death and MI. XIENCE V® USA 5

Multivariable Cox Regression - Methods Model: includes clinical, angiographic and procedural variables. In patients with more than one lesion, the most severe vessel/lesion was chosen. The multivariable model was created using stepwise regression, where variables were entered into the model either through clinical judgement or at the 0.05 significance level and removed at the 0.05 level (from the Wald chi-square statistic). Variables were eligible for inclusion in the multivariable model-building process if the variable was present for 90% of the subjects in the analyses, had a univariate p-value <0.05, and, if highly correlated with another variable (r>0.5 and p<0.05), had the higher level of significance.

Clinical, Angiographic, and Procedural Variables of the Predictor Analysis 16 Demographic and Clinical: Age Gender Current Tobacco Use Diabetes Requiring Rx Hypertension Requiring Rx Hypercholesterolemia Requiring Rx Prior CABG Prior CABG or Multiple Diseased Vessels* Prior PCI CCS III or IV Prior MI Acute Myocardial Infarction Renal Insufficiency Stroke Left Ventricular Ejection Fraction Number of Diseased Vessels 12 Angiographic: Pre-procedure %DS Pre-procedure TIMI Target Lesion Length In Stent Restenosis Bifurcation Ostial ACC/AHA Lesion Class CTO* Target Vessel: LAD Target Vessel: LM Target Vessel Graft Heavy Calcification 12 Procedural: Pre Dilatation Post Dilatation Maximum Balloon Pressure 2.5mm Stent(s) Implanted Number of Treated Lesions Number of Treated Vessels Bailout Stent Usage Number of Stent Implanted Total Length of All Stents DAPT Interruption within 30 Days Post Procedure DAPT Interruption after 30 Days Post Procedure Permanent DAPT Discontinuation between 1 to 3 Years* Note: Prior bracytherapy was removed as a demographic/clinical variable. *Variables not present in the original 1-year Naidu et al. analysis XIENCE V® USA

Study Populations Patient Populations Standard Risk Overall Population A total of 5034 patients were consecutively enrolled from 162 U.S. sites. In addition to an analysis of the overall (all-comer) population, outcomes are also reported for patients who are defined as standard risk. Patient Populations Overall Population Includes all available long-term follow-up patients Standard Risk lesion length ≤ 28 mm, reference vessel diameter between 2.5 mm and 4.25 mm, patients considered on-label and near on-label XIENCE V® USA

Patient Flow Long-Term Follow-up Cohort N=5034 14 Patients Transferred to HCRI DAPT Study Long-Term Follow-up Standard Risk Cohort N=1871 Long-Term Follow-up Overall Cohort N=5020 282 Early Terminations 108 Deaths 119 Lost to follow-up 41 Withdrew Consent 9 Withdrawn by Physician 5 Other Follow-up at 1 year N=1782 (95.2%) Follow-up at 1 year N=4738 (94.4%) 236 Early Terminations 123 Deaths 84 Lost to follow-up 11 Withdrew Consent 14 Withdrawn by Physician 4 Other Follow-up at 2 years N=1726 (92.3%) Follow-up at 2 years N=4502 (89.7%) 154 Early Terminations 117 Deaths 2 Lost to follow-up 25 Withdrew Consent 9 Withdrawn by Physician 1 Other Follow-up at 3 years N=1678 (89.7%) Follow-up at 3 years N=4348 (86.6%) XIENCE V® USA

Baseline Patient Characteristics Overall (N = 5020) Standard Risk (N = 1871) Age (yrs) 64.8 64.3 Male (%) 68.8 66.3 Diabetes (%) 35.7 31.0 Prior MI (%) 30.8 24.8 2 or More Vessel Disease (%) 40.8 30.7 AMI (%) 16.0 NA Unstable Angina (%) 22.4 24.7 LVEF < 30% (%) 3.3 Renal Insufficiency (%) 11.1 Prior Cardiac Intervention (%) PCI (%) CABG (%) 51.3 40.1 15.5 44.2 36.6 8.8 N: total number of patients; NA: not applicable since patients were excluded from the Standard Risk cohort XIENCE V® USA 10

Lesion and Procedure Characteristics Overall (L = 7024) Standard Risk (L = 2309) Graft Lesion (%) 4.8 NA Left Main Lesion (%) 1.6 B2/C Lesion (%) 49.3 35.6 Restenosis (%) 9.4 Chronic Total Occlusion (%) 2.5 Bifurcation Lesion (%) 9.2 1.8 Ostial Lesion (%) 11.8 Lesion Length (mm) 16.0 14.2 # of Lesions Treated 1.4 1.2 # of Stents per Lesion 1.1 Stent Length per Lesion (mm) 21.2 18.6 Direct Stenting (%) 38.8 44.6 L: total number of lesions; NA: not applicable since patients were excluded from the Standard Risk cohort XIENCE V® USA 11

DAPT Usage and Stent Thrombosis Similar dual anti-platelet therapy (DAPT) usage at 3 years between the Overall population and Standard Risk groups Low overall rate of very late (ARC definite/probable) ST between 1-3 years Overall Population 53.1% (2666/5020) patients on DAPT at 3 yrs Standard Risk 54.8% (1026/1871) patients on DAPT at 3 yrs Very late definite/probable ST Rate (1-3 yrs) 0.22% Very late definite/probable ST Rate (1-3 yrs) 0.06% DAPT usage at 1 year: 81.5% (overall) and 82.8% (standard risk) DAPT usage at 2 years: 61.9% (overall) and 63.2% (standard risk) XIENCE V® USA

ARC Definite/Probable Stent Thrombosis through 3 years Overall Real-World Population Standard Risk Stent Thrombosis (%) 1.08% 0.38% Years Overall 5020 4665 4451 4310 Standard Risk 1871 1765 1715 1670 XIENCE V® USA

Real-World Landmarked ARC Definite/Probable Stent Thrombosis from 1 to 3 years Overall Real-World Population 10 Stent Thrombosis Events from 1 to 3 years With only 53.1% of the overall population on DAPT at 3 years, DAPT discontinuation was not a predictor of ST. Stent Thrombosis (%) 0.22% Years Overall 4665 4470 4328 XIENCE V® USA

Multivariable Predictors of ARC ST from 1 to 3 Years in the Overall Population Variables P Value Hazard Ratio [95% CI] Target Vessel Graft (Yes vs No) 0.003 19.47 [2.73, 139.1] 0.001 0.1 10 1000 XIENCE V® USA

Landmarked Clinical Outcomes from 1 to 3 years* Overall Real- World (N = 5020) Standard Risk (N = 1871) Target Lesion Failure (ARC) 8.6% 5.6% Cardiac Death or MI (ARC) 4.5% 2.4% Target Lesion Revascularization 4.1% *Rates are from Kaplan-Meier estimates XIENCE V® USA

Multivariable Predictors of Cardiac Death or MI (ARC) from 1 to 3 Years in the Overall Population Variables P Value Hazard Ratio [95% CI] Prior CABG (Yes vs. No) 0.01 2.01 [1.16, 3.49] Renal Insufficiency (Yes vs. No) 0.04 1.91 [1.02, 3.55] Prior MI (Yes vs. No) 1.91 [1.15, 3.15] Diabetes Requiring Rx (Yes vs. No) 1.74 [1.04, 2.92] 0.10 1 10 Note: All resulting variables were demographic/clinical

Conclusions In this large, real-world population of complex patient and lesion cohorts, neither DAPT interruption before or after 30 days nor permanent DAPT discontinuation after 1 year were predictors of stent thrombosis between 1-3 years. The only predictor of stent thrombosis was target vessel graft. Predictors of cardiac death or MI were associated exclusively with the patient’s disease state (including prior CABG, renal insufficiency, prior MI, diabetes requiring Rx). The overall results demonstrate continued safety and effectiveness of XIENCE V through 3 years in a real-world setting.