1. 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

2. 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.

3. 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

4. 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

5. 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)

6. 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

7. 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

8. 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

9. 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

10. 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

11. 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

12. 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

13. 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] : [0.02,1.37]; 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