1. A Randomized Comparison of a Sirolimus-eluting Stent with Biodegradable Polymer versus an Everolimus-eluting Stent with a Durable Polymer for Percutaneous Coronary Revascularization Thomas Pilgrim, MD Swiss Cardiovascular Center Bern University Hospital, Switzerland

2. Overall (I-squared = 0·0%, p=0·92) LEADERS 4 years fup ISAR-TEST 4 3 years fup ISAR-TEST 3 2 years fup 20/857 9/1299 1/202 32/850 9/652 2/202 0·58 (0·37, 0·93) 0·62 (0·36, 1·08) 0·50 (0·20, 1·26) 0·50 (0·05, 5·47) 10·10·2250·5 Favours biodegradable polymer DES Favours durable polymer SES BP-DESDP-SES RR (95% CI) Definite ST A Meta-Analysis of Biodegradable Polymer DES versus Durable Polymer Sirolimus Eluting Stents Stefanini G et al. Lancet 2011; 378:1940-8 Overall (I-squared = 0·0%, p=0·79) LEADERS 4 years fup ISAR-TEST 4 3 years fup ISAR-TEST 3 2 years fup 88/857 168/1299 17/202 111/850 95/652 21/202 0·84 (0·71, 0·99) 0·79 (0·60, 1·02) 0·89 (0·70, 1·12) 0·81 (0·44, 1·49) TLR Favours biodegradable polymer DES Favours durable polymer SES 10·10·2250·5 BP-DESDP-SES RR (95% CI)

3. Biodegradable Polymer Based DES Platforms Sirolimus – ISAR TEST Biolimus A9 – BioMatrix Nobori, Axxess, XTENT Sirolimus – ORSIRO Sirolimus – Genous Bioengineered R Stent Everolimus - SYNERGYMyolimus – ELIXIR

4. Orsiro 1 Hybrid Sirolimus Eluting Stent System Passive component: PROBIO Silicon carbide 2 layer that encapsulates the stent surface, reducing ion release Active component: BIOlute PLLA 3 bioabsorbable polymer matrix Sirolimus (1.4 µg/mm 2 ) Controlled drug release out to 3 months Asymmetric coating with greater drug dose on abluminal side (Ablumial thickness 7.4 µm) Stent platform: PRO-Kinetic Energy Cobalt Chromium, L-605 60 µm struts 1 Manufactured and distributed by BIOTRONIK 2 aSiC:H amorphous silicon carbide 3 Poly-L-lactide In vivo drug release in minipig coronary arteries 0 10 20 30 40 50 60 70 80 90 100 0102030405060708090100 % Drug Release Time (days) Source: Data on file at BIOTRONIK

5. BIOSCIENCE Trial NCT01443104 Primary endpoint: Target lesion failure defined as the composite of cardiac death, target vessel myocardial infarction, and clinically-driven target lesion revascularization at 12 months 2100 Patients Orsiro ® Stent system Sirolimus-eluting stent with a biodegradable polymer Xience PRIME ® stent Everolimus-eluting stent with a durable polymer 1:1 Prospective multi-center randomized “all-comers” trial with a non-inferiority design

6. Inclusion Criteria 1Age ≥18 years; 2Symptomatic coronary artery disease including patients with chronic stable angina, silent ischemia, and acute coronary syndromes including NSTE-ACS and STE-ACS; 3Presence of one or more coronary artery stenoses >50% in a native coronary artery or a saphenous bypass graft which can be treated with a stent ranging in diameter from 2.25 to 4.0 mm and can be covered with one or multiple stents; 4No limitation on the number of treated lesions, and vessels, and lesion length

7. Exclusion Criteria 1Pregnancy; 2Known intolerance to aspirin, clopidogrel, heparin, stainless steel, Sirolimus, Everolimus or contrast material; 3Inability to provide informed consent; 4Currently participating in another trial before reaching first endpoint; 5Planned surgery within 6 months of PCI unless dual antiplatelet therapy is maintained throughout the peri-surgical period

8. Follow-up Clinical follow-up (visit) at 12 months; Telephone follow-up at 30 days, 1, 2, and 5 years

9. Primary Endpoint Target lesion failure (TLF) in the overall population, defined as the composite of cardiac death, target vessel Q-wave or non-Q wave myocardial infarction (MI) (i.e., Q-wave MI that cannot be attributed to a non-target vessel), clinically driven target lesion revascularization (TLR) and emergent coronary artery bypass grafting (CABG) within 12 months.

10. Secondary Endpoints Clinically indicated and not clinically indicated target lesion revascularization (TLR) at 30 days, 1, 2 and 5 years. Clinically indicated and not clinically indicated target vessel revascularization (TVR) at 30 days, 1, 2, and 5 years. TLF composite of cardiac death, target vessel Q-wave or non-Q wave myocardial infarction (MI) (i.e., Q-wave MI that cannot be attributed to a non-target vessel), clinically driven target lesion revascularization (TLR) and emergent coronary artery bypass grafting (CABG)at 30 days, 2, and 5 years. Target Vessel Failure (TVF) at 30 days, 1, 2, and 5 years. Cardiac death at 30 days, 1, 2, and 5 years. All deaths (cardiac and non-cardiac) at 30 days, 1, 2, and 5 years. Myocardial infarction (Q-wave and NQWMI) at 30 days, 1, 2, and 5 years. Definite stent thrombosis at 30 days, 1, 2, 3and 5 years. Definite or probable stent thrombosis at 30 days, 1, 2, and 5 years. Device success, lesion success and procedural success (see definitions).

11. Time Schedule EventScreen Procedur e Post -Procedure to Hospital D/c 30 Days1 Yr2 Yrs5 Yrs Type of contactPhoneVisitPhone Inclusion/ exclusion Criteria X Informed consentX Physical examination X Medical and Cardiac history X Anginal StatusXXXXXX CBC, blood chemistry, lipids, X CK, CK-MBXX TroponinXX 12 lead ECGXX Medication regimen XXXXXXX Adverse event and Severe Adverse Event monitoring XXXXXX

12. Contacts Dr. med. Thomas Pilgrim Invasive Kardiologie, Inselspital Bern thomas.pilgrim@insel.ch 076 548 44 11