Two-year clinical outcomes in the EVOLVE FHU trial: A randomized evaluation of a novel bioabsorbable polymer-coated, everolimus-eluting stent Ian Meredith MonashHeart, Clayton, Victoria, Australia Stefan Verheye, Leif Thuesen, Monica Masotti, Adrian Banning, Iwar Sjögren, Rod Stables, Dominic Allocco, and Keith Dawkins on behalf of the EVOLVE investigators Hot Line - Trial Updates and Registries Wednesday 22nd May 2013, 14:10 to 15:10 Room 242AB

Disclosures Honoraria for speaking/consultancy from Boston Scientific

Introduction: Bioabsorbable polymer Durable polymer coatings on drug-eluting stents have been associated with chronic inflammation and impaired healing. Potential advantages of bioabsorbable polymer stents: Reduced polymer load Short-term polymer exposure may Decrease risk of late events including ST and TLR Reduce required duration of DAPT and risk if interrupted

Stent Strut Cross Sections The SYNERGY stent Bioabsorbable polymer (PLGA) Everolimus applied only to the abluminal surface (rollcoat) Thin strut (74µm) platinum chromium stent Stent Strut Cross Sections 81μm 74μm Arterial Wall

Trial Design and Methods Patients with de novo native coronary lesions ≤ 28 mm in length, RVD ≥2.25 mm ≤ 3.5, %DS>50 (excluded LM disease, CTO, AMI or recent MI) Randomized 1:1:1 at 29 sites (Europe, Australia, New Zealand) PROMUS Element N=98 SYNERGY N=94 SYNERGY ½ Dose N=99 Single-blind, noninferiority design Primary Clinical Endpoint: TLF (TV-CD, TV-MI, or TLR) at 30 days Primary Angiographic Endpoint: In-stent late loss at 6 months Per protocol patients were treated with clopidogrel, ticlopidine or prasugrel for at least 6 months following the index procedure Meredith et al, JACC 2012

Trial Design and Methods All Patients with de novo coronary lesions (Intent-to-treat) N=291 PROMUS Element N=98 SYNERGY N=94 SYNERGY ½ Dose N=99 1-year Follow-up N=98 1-year Follow-up N=92 1-year Follow-up N=95 2-year Follow-up N=98/98 (100%) 2-year Follow-up* N=90/92 (97.8%) 2-year Follow-up N=93/99 (93.9%) *At 2-years follow-up, the prespecified safety analysis patient population, which included only those patients treated with a study stent, was analysed. Two SYNERGY patients were not included in safety analysis as they did not receive the study stent.

Primary Endpoints Noninferiority was proven because the upper 95.2% confidence bound of the difference in 6-month late loss is <0.20 for both SYNERGY stents Intent-to-treat; Mean + Standard Deviation; *P values for superiority comparison Meredith et al, JACC 2012

6-month IVUS Outcomes Rates of persistent and late-acquired malapposition were similar between the 3 groups Intent-to-treat; Mean + Standard Deviation Verheye PCR 2012

1-year Clinical Outcomes PROMUS Element (n=98) SYNERGY (n=94) SYNERGY ½ Dose (n=99) Components of Target Lesion Failure 5.1 5.1 Patients, % 4.4 4.2 3.3 3.2 1.1 1.1 TLF TLR MI* Cardiac Death* ST Intent-to-treat; P values are versus PROMUS Element (Fisher exact test); ; All p-values are >0.05; *Target Vessel Related Meredith PCR 2012

Target Lesion Revascularisation 2-year Follow-up PE vs SYNERGY HR 0.18 [0.02, 1.47] P=0.07 PE vs SYNERGY ½ HR 0.17 [0.02, 1.41] P=0.06 20 Protocol-required angiogram TLR, % 6.1 1.1 1.0 6 12 24 Months Numbers at risk PE 98 93 SYNERGY 92 90 SYNERGY ½ Dose 99 97 94 69 65 63 Safety Population; KM Event Rate; log-rank P values

Target Lesion Failure 2-year Follow-up PE vs SYNERGY HR 0.89 [0.27, 2.93] P=0.85 PE vs SYNERGY ½ HR 0.87 [0.26, 2.83] P=0.81 20 Protocol-required angiogram TLF, % 6.1 5.5 5.2 6 12 24 Months Numbers at risk PE 98 93 SYNERGY 92 91 89 SYNERGY ½ Dose 99 94 69 64 62 Safety Population; KM Event Rate; log-rank P values

Death/MI/TVR 2-year Follow-up PE vs SYNERGY HR 0.84 [0.33, 2.14] P=0.72 PE vs SYNERGY ½ HR 1.03 [0.43, 2.48] P=0.94 20 Protocol-required angiogram 10.4 Death/MI/TVR, % 10.2 8.7 6 12 24 Months Numbers at risk PE 98 89 SYNERGY 92 91 87 SYNERGY ½ Dose 99 94 88 66 63 61 Safety Population; KM Event Rate; log-rank P values

2-year Clinical Outcomes PROMUS Element SYNERGY SYNERGY ½ Dose Year 1 Year 2 Year 1 Year 1 Components of Target Lesion Failure 6.1 6.1 5.5 5.2 Patients, % 3.3 3.0 1.1 1.0 1.1 1.1 TLF TLR MI* Cardiac Death* ST Safety Population; KM Event Rates; All p-values are >0.05; *Target Vessel Related

Additional Two-year Outcomes PROMUS Element n=98 SYNERGY n=92 P value SYNERGY ½ Dose n=99 All-cause death 0.0% (0) 4.4% (4) 0.04 3.2% (3) 0.07 - Cardiac 1.1% (1) 0.29 0.30 - Non-cardiac 3.3% (3) 2.2% (2) 0.15 Any MI 3.0% (3) 0.08 - Q-wave Undef - Non-Q-wave Safety Population; KM Event Rates, P values are versus PROMUS Element (Fisher exact test)

(Post index procedure) Deaths in EVOLVE Day (Post index procedure) Cause 191 Multiple injuries sustained in motor bike accident 364 Broken ribs and pneumothorax after a fall leading to respiratory failure 373 Diffuse metastatic breast carcinoma 472 Death due to unknown cause (considered a cardiac death) 577 Right lung carcinoma 593 Right middle cerebral artery infarct 678

Antiplatelet Medication Usage Discharge 1 year 2 years Patients, % 95.9 97.7 98.9 45.9 45.3 42.2 41.8 44.2 41.1 ASA Thienopyridines DAPT PROMUS Element (n=98) SYNERGY ½ Dose (n=99) SYNERGY (n=92)

Conclusions and Significance In this prospective, randomized, multicentre, first human use trial, the 2 dose formulations of the SYNERGY stent were non-inferior to the PROMUS Element stent for the primary angiographic endpoint of in- stent late loss at 6 months At 2 years, no significant differences between groups with for TLF, cardiac death or MI Trend toward lower rates of revascularisation with SYNERGY vs PROMUS Element No incidence of stent thrombosis in any group at 2 years These results support the safety and efficacy of the novel abluminal bioabsorbable polymer SYNERGY everolimus-eluting stent for the treatment of patients with de novo coronary artery disease Additional research is needed to evaluate clinical event rates and the potential for dual antiplatelet therapy reduction with this novel stent