Durable Polymer DES: 5 Year Outcomes RESOLUTE Update Sigmund Silber, MD FESC, FACC, FAHA Heart Center at the Isar Munich, Germany On Behalf of the RESOLUTE Study Group

Disclosure Statement of Financial Interest I, Sigmund Silber, MD, DO NOT have a financial interest/arrangement or affiliation with one or more organizations that could be perceived as a real or apparent conflict of interest in the context of the subject of this presentation.

The RESOLUTE Program: 1 Meredith IT, et al. EuroIntervention. 2010;5: Serruys PW, et al. N Engl J Med. 2010;363: Silber S, et al. Lancet. 2011;377: Neumann FJ, et al. EuroIntervention. 2012;7(10): Belardi JA, et al. J Interv Cardiol. 2013;26(5): Yeung AC, et al. JACC. 2011;57: Lee M, et al. Am J Cardiol. 2013;112(9): Xu B, et al. JACC Cardiovasc Interv. 2013;6(7): Qiao S, et al. Am J Cardiol. 2014;113(4): RESOLUTE 1 Non-RCT First-in-Human (R=139) 5 yr RESOLUTE AC 2,3 1:1 Randomized vs. Xience V ™ EES (R=1140; X=1152) 5 yr 2.25 – 4.0 mm Non-RCT vs. Hx Control (R=1402) 5 yr RESOLUTE US – 3.5 mm Non-RCT (R=100) vs. Hx Control RESOLUTE Japan 5 yr 1:1 RCT vs. Taxus ™ PES (R=200; T=200) R-China RCT 8 3 yr Non-RCT Observational (R=2349) 3 yr RESOLUTE Int 4,5 R-China Registry 9 Non-RCT Observational (R=1800) 2 yr R-Japan SVS 2.25 Non-RCT vs. PG (R=65) 3 yr 38 mm sub-study Non-RCT vs. PG (R=114) 3 yr RESOLUTE US 7 Available follow-up RESOLUTE Asia 7 Non-RCT Observational (R=312) 2 yr R

RESOLUTE All Comers Randomized Trial

TLF (Target Lesion Failure) is defined as cardiac death, TVMI, or clinically driven TLR. Time After Initial Procedure (years) 0132 Cumulative Incidence of TLF (%) % 17.1% Log rank P = 0.65 Resolute ™ ZES (N = 1140) Xience V ™ EES (N = 1152) Primary endpoint P non-inferiority < % 8.2% No. at risk Resolute Xience V RESOLUTE All Comers-RCT– 5 Years Target Lesion Failure (TLF)

Time After Initial Procedure (years) 0132 Cumulative Incidence of ARC Definite ST (%) % 1.62% No. at risk Resolute Xience V Log rank P = 0.08 Resolute ™ ZES (N = 1140) Xience V ™ EES (N = 1152) 5 RESOLUTE All Comers-RCT– 5 Years Stent Thrombosis - Definite

Time After Initial Procedure (years) 132 Cumulative Incidence of Very Late ARC Definite ST (%) % 0.47% Log rank P = 0.76 Resolute ™ ZES (N = 1140) Xience V ™ EES (N = 1152) No. at risk Resolute Xience V RESOLUTE All Comers-RCT– 5 Years Very Late Stent Thrombosis - Definite

Eurointervention 10: (2015)

The RESOLUTE Pooled Program: 7618 Patients Included in this Pooled Analysis 1 Meredith IT, et al. EuroIntervention. 2010;5: Serruys PW, et al. N Engl J Med. 2010;363: Silber S, et al. Lancet. 2011;377: Neumann FJ, et al. EuroIntervention. 2012;7(10): Belardi JA, et al. J Interv Cardiol. 2013;26(5): Yeung AC, et al. JACC. 2011;57: Lee M, et al. Am J Cardiol. 2013;112(9): Xu B, et al. JACC Cardiovasc Interv. 2013;6(7): Qiao S, et al. Am J Cardiol. 2014;113(4): RESOLUTE 1 Non-RCT First-in-Human (R=139) 5 yr RESOLUTE AC 2,3 1:1 Randomized vs. Xience V ™ EES (R=1140; X=1152) 5 yr 2.25 – 4.0 mm Non-RCT vs. Hx Control (R=1402) 5 yr RESOLUTE US – 3.5 mm Non-RCT (R=100) vs. Hx Control RESOLUTE Japan 5 yr 1:1 RCT vs. Taxus ™ PES (R=200; T=200) R-China RCT 8 3 yr Non-RCT Observational (R=2349) 3 yr RESOLUTE Int 4,5 R-China Registry 9 Non-RCT Observational (R=1800) 2 yr R-Japan SVS 2.25 Non-RCT vs. PG (R=65) 3 yr 38 mm sub-study Non-RCT vs. PG (R=114) 3 yr RESOLUTE US 7 Available follow-up RESOLUTE Asia 7 Non-RCT Observational (R=312) 2 yr R

This pooled analysis includes all trials within the RESOLUTE Global Clinical Program, including regulatory trials with 100% monitoring, all with high rates of follow-up. Patient level data of all 7618 Resolute patients were pooled, including data to the latest available follow-up of each trial. Kaplan Meier cumulative incidence out to 5 year follow-up was calculated. Strengths: All trials were prospectively performed and event definitions across studies were consistent. The independent clinical event adjudication was harmonized across all studies. Limitations: post-hoc analysis RESOLUTE Pooled Program Methods

%N = 7618 Pts Age (yr) 63.0 ± 11.0 Male75.4 Diabetes mellitus30.4 IDDM6.7 Hypertension71.0 Hyperlipidemia62.3 Current smoker26.4 Family history29.1 Prior MI29.2 Prior PCI25.8 Prior CABG6.3 Cardiac Status: Stable angina33.0 Unstable angina38.1 All myocardial infarction25.9 Acute coronary syndrome52.4 RESOLUTE Pooled Program Baseline Patient Characteristics

%N = 7618 Pts Age (yr) 63.0 ± 11.0 Male75.4 Diabetes mellitus30.4 IDDM6.7 Hypertension71.0 Hyperlipidemia62.3 Current smoker26.4 Family history29.1 Prior MI29.2 Prior PCI25.8 Prior CABG6.3 Cardiac Status: Stable angina33.0 Unstable angina38.1 All myocardial infarction25.9 Acute coronary syndrome52.4 RESOLUTE Pooled Program Baseline Patient Characteristics

RESOLUTE Pooled Program Lesion and Procedure Characteristics

Cutlip DE, et al. Circulation. 2007; 115: RESOLUTE Pooled Program – 5 Years Individual Components of the Device-Oriented Endpoint

Device Oriented Composite Endpoint Target Lesion Failure (TLF) Cardiac Death Target Vessel Myocardial Infarction (TV- MI) Target Lesion Revascularization (clinically indicated, TLR) Patient Oriented Composite Endpoint (POCE) All Deaths All Myocardial Infarctions All Revascularizations Cutlip DE, et al. Circulation. 2007; 115: RESOLUTE Pooled Program Definition of Composite Endpoints

Cutlip DE, et al. Circulation. 2007; 115: RESOLUTE Pooled Program – 5 Years Device-Oriented vs. Patient-Oriented Endpoint

RESOLUTE Pooled Program – 5 Years Definite Stent Thrombosis (ARC)

RESOLUTE Pooled Program – 5 Years Definite / Probable Stent Thrombosis (ARC)

RESOLUTE Pooled Program – 5 Years Very Late Stent Thrombosis (Definite / Probable, ARC)

RESOLUTE Pooled Program – 5 Years DAPT Usage - Overall

RESOLUTE Pooled Program – 5 Years DAPT Usage – Individual Trials

RESOLUTE 5 Years – Conclusions All Comers Randomized Trial: The follow-up rate at 5 years was extremely high (98.5%), further supporting the reliability of these long term study outcomes in an all-comer patient population. In this predominantly complex patient population, the Resolute ZES and Xience V EES remained clinically equivalent through 5 years (TLF 17.1% vs. 16.3%, p = 0.65). Despite that only ~10% of patients were on DAPT at 5 years, the incidence of very late stent thrombosis is low and similar between the Resolute ZES and the Xience V EES (def/prob ST 0.84% vs. 1.03%, P = 0.66). The results are consistent with the TWENTE trial.

The current analysis of 7618 patients is the largest and longest dataset to date of Resolute patients evaluated. While the complexity of patients varied by study, approximately half of all patients had one or more complex patient characteristics. Long-term follow-up of current generation DES remains critically important to evaluate if there is any increased risk over time of low frequency events. In this pooled analysis, we did not observe any concerns of long term safety associated with the Resolute stent. The event rates were stable through long-term follow-up. In particular, the rate of very late ST (>1 yr, definite/probable) is low at 0.5% out to 5 years. Significant differences were observed in DAPT duration between trials and geographies, reflective of different clinical practices around the world. Over 5 years, more than half of the adverse events were not device (= stent) related, indicating that we still need better general treatment options for patients with coronary artery disease - even after stenting the culprit lesion(s). RESOLUTE 5 Years – Conclusions Pooled Clinical Program: