Late Clinical Outcomes after Bioresorbable or Permanent Polymer Everolimus-Eluting Stents: 2-Year Results from the EVOLVE II Randomized Trial Dean J. Kereiakes The Christ Hospital Heart and Vascular Center/ The Lindner Research Center Cincinnati, OH Dean J. Kereiakes, Ian T. Meredith, Stephan Windecker, Ameer Kabour, Alain Bouchard, Annapoorna S. Kini, Luc Janssens, Michael Foster, Robert Stoler, Thomas Stuckey, Wayne Batchelor, Thomas Christen, Dominic J. Allocco, Keith D. Dawkins on behalf of the EVOLVE II investigators

Disclosure Statement of Financial Interest Within the past 12 months, I or my spouse/partner have had a financial interest/arrangement or affiliation with the organization(s) listed below. Affiliation/Financial Relationship Company Modest Consulting Fees Significant Consulting Fees Major Stock Shareholder/Equity HCRI Boston Scientific Abbott Vascular Svelte Medical Systems, Inc. Janssen Research & Development LLC Sanofi-Aventis U.S. LLC Ablative Solutions, Inc.

Background Permanent polymers have been associated with inflammation, delayed healing, neoatherosclerosis and thrombosis risk late following DES deployment Bioabsorbable polymers were designed to enhance stent healing but there are few data available on longer term outcomes Clinical outcome differences between bioresorbable and permanent polymer DES may become evident during longer term follow-up

SYNERGY Stent SYNERGY Stent Platform Polymer Coating Drug Drug & Polymer Coating Abluminal (4μm) Everolimus Drug PLGA Polymer SEM of coating (x5000) Luminal Platform Platinum chromium 74 μm (0.0029in) Polymer Coating PLGA Abluminal 4 µm thick 85:15 ratio Drug Everolimus 100 μg/cm2

SYNERGY Stent Synchronous Drug Release & Polymer Absorption Preclinical evaluation in porcine model Everolimus Arterial Tissue Concentration ng/mg Everolimus Mass Remaining PLGA Mass Remaining Limit of Quantitation (LOQ)

Patient Disposition and Antiplatelet Medication Usage : EVOLVE II Intent-to-treat Patients N=1684 PROMUS Element Plus N=838 SYNERGY N=846 1-year Follow-up N=806 (96.2%) 1-year Follow-up N=831 (98.2%) ASA DAPT PE+ SYN 1 year 97.5% 98.3% 84.8% 87.0% 2 years 96.3% 97.3% 50.2% 47.6% 2-year Follow-up N=796 (95.0%) 2-year Follow-up N=816 (96.5%) *After the first year of follow-up, only patients who received study stents were followed (No study stent implanted: PROMUS ELEMENT Plus arm n=9 and SYNERGY arm n=3). 2 year ASA: P=0.27; DAPT P=0.31 Kereiakes et al. Circ Cardiovasc Interv 2015

EVOLVE II TLF at 1 and 2 years PROMUS Element Plus vs SYNERGY 1 Endpoint: 12 months ITT Pnoninferiority=0.0005 16 2 years HR 1.10 [0.79, 1.52] P=0.57 12 TLF (%) 9.4% 6.7% 8.5% 8 4 6.5% No. at risk 6 12 24 PE+ 838 790 772 538 SYNERGY 846 807 794 553 Months ITT Population; Patients who did not receive a study stent were censored at 1 year; KM Event Rates; log-rank P values

TLF and Components at 2 years Components of TLF ITT Population; Patients who did not receive a study stent were censored at 1 year; KM Event Rates; Per protocol spontaneous MI is defined as rise and/or fall of cardiac biomarkers with ≥1 value >99th percentile of the URL + evidence of myocardial ischemia. Peri-PCI MI is defined as ≥1 of the following: i) biomarker elevations within 48 hours of PCI (based on CK-MB >3X URL), ii) new pathological Q waves, or iii) autopsy evidence of acute MI

Additional Outcomes at 2 years P=0.55 P=0.65 P=0.80 P=0.82 P=0.57 P=0.17 P=0.61 ITT Population; Patients who did not receive a study stent were censored at 1 year; KM Event Rates

Stent Thrombosis at 2 years Definite/Probable : ITT Population Acute (≤1 d) Subacute (2-30 d) Late (30 d – 1 y) Very Late (1 – 2 y) N=5 (2 Definite/3 Probable) N=1 (Def) 0.8% (N=6) P=0.31 N=2 (Definite) N=1 (Prob) 0.4% (N=3) Other details? No definite ST in the SYNERGY arm after 24 hours

Stent Thrombosis at 2 years PROMUS Element Plus vs SYNERGY HR 0.50 [0.12, 1.98] P=0.31 4 3 Definite/Probable ST (%) 2 1 0.8% 0.4% No. at risk 6 12 24 PE+ 838 820 810 575 SYNERGY 846 837 829 585 Months ITT; Patients who did not receive a study stent were censored at 1 year; KM Event Rate; log-rank P values

ST Landmark Analysis Definite/Probable ST after 24 hours PROMUS Element Plus vs SYNERGY >24 h Landmark HR 0.16 [0.02, 1.37] P=0.056 4 3 Definite/Probable ST (%) 2 1 0.8% * 0.1% 1d 6 mo 12 mo 24 mo ‡Day 715 – Definite ST: Patient was not compliant to aspirin and was not taking at P2Y12 inhibitor at time of presentation ST occurring between 0 and 1 years have been previously reported in Kereiakes et al. Circ Cardiovasc Interv 2015 ITT; Patients who did not receive a study stent were censored at 1 year; KM Event Rate; log-rank P values

Conclusions and Significance Two year follow-up from the EVOLVE II trial supports continued safety and efficacy of the SYNERGY stent Definite/probable ST was infrequent after SYNERGY and beyond 24 hours, only 1 probable ST on day 6 (HR [95%CI] : 0.16 [0.02,1.37]; P=0.056 vs PROMUS Element Plus) occurred which suggests that the early dissolution of the abluminal bioresorbable polymer coating and/or luminal exposure of platinum chromium metal alloy with SYNERGY (vs. PVDF) may provide improved vessel healing and thrombus resistance Longer term data in more complex patient populations will provide further insights into stent healing and very late clinical events following SYNERGY stent implantation