1. ISAR-LEFT MAIN 2 Randomized Trial Zotarolimus- vs. Everolimus-Eluting Stents for Treatment of Unprotected Left Main Coronary Artery Lesions Julinda Mehilli, MD Klinikum der Universitaet Munich Deutsches Herzzentrum Munich Germany

2. Disclosure Statement of Financial Interest Lecture fees Abbott Vascular Daichii Sankyo/Lilly The Medicines Terumo 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 RelationshipCompany

3. PCI vs. CABG Surgery for uLMCA Meta-analysis of Randomized Controlled Studies Capodanno et al., J Am Coll Cardiol 2011 Similar Risk of Death or Myocardial Infarction Higher Risk of Revascularization

4. Mehilli et al., J Am Coll Cardiol 2009 First Generation DES for uLMCA Similar Clinical & Angiographic Performance ISAR-LEFT MAIN

5. Kim YH et al., J Am Coll Cardiol, Interv 2012 Second Generation DES for uLMCA Improved Clinical Performance Ischemia-driven TVR MACE PRECOMBAT 2 trial

6. Serruys et al., New Engl J Med 2010 Second Generation DES for All-Comers Resolute All Comers trial

7. ISAR-LEFT MAIN 2 DESIGN: Randomized, multi-center trial OBJECTIVE: To evaluate the relative performance of two 2 nd generations DES – zotarolimus- and everolimus-eluting stents – in patients with uLMCA lesions STEERING COMMITTEE Adnan Kastrati, MD ( Chair) Julinda Mehilli, MD (principal investigator) Josef Dirschinger, MD PARTICIPATING CENTERS Deutsches Herzzentrum & Klinikum rechts der Isar, Munich, Germany PI: J. Mehilli & K-L Laugwitz Bad Segeberger Kliniken, Bad Segeberg, Germany PI: G Richart Department of Cardiology, University of Ferrara, Italy PI: M Valgimigli

8. Patients with ischemic symptoms or evidence of myocardial ischemia in the presence of ≥50 % stenosis located in unprotected LMCA who are unable to undergo CABG because of cardiac surgeons’ refusal (poor surgical candidates) or their own unwillingness Inclusion Criteria

9. Age < 18 years Cardiogenic shock ST-Elevation Acute Myocardial Infarction In-stent Restenosis Prior coronary artery bypass surgery Malignancies with life expectancy <1 year Planned staged PCI within 30 days from index PCI Planned elective surgical procedure necessitating interruption of clopidogrel during the first six months after PCI Pregnancy Exclusion Criteria

10. Incidence of major adverse cardiac events defined as the composite of death myocardial infarction target lesion revascularization at 1-year follow-up Primary Endpoint

11. Angiographic restenosis at 8-month FU angiogram, defined as diameter stenosis ≥50% measured by QCA in the area from left main ostium to 5-mm proximal segments of LAD, LCx as well as of R. intermedius if the latter has a reference diameter >2 mm left main area analysis Secondary Endpoints ARC-defined stent thrombosis at 1-year follow-up

12. Hypothesis: Endeavor Resolute stent is not inferior to Xience stent in terms of major adverse cardiac events Assumptions: Incidence of MACE 25% in both stent groups Margin of non-inferiority 9% Power of 80%  -level of 0.05 Rate of lost to follow-up 5% Planed number of patients for each group: 300 Sample Size Calculation

13. ISAR-LEFT MAIN 2 Trial 650 patients with uLMCA lesions pre-treated with 600 mg clopidogrel Angiographic follow-up at 8 months in 73% (N=237) Zotarolimus-eluting stent (Endeavor Resolute) N= 324 Everolimus-eluting stent (Xience) N= 326 Angiographic follow-up at 8 months in 69% (N=226) Clinical follow-up at 12 months in 100% (N=324) Clinical follow-up at 12 months in 100% (N=326)

14. Baseline Characteristics Resolute n=324 Xience n=326 Age, years 69.4±10.4 70.2 ±9.4 Women, % 27 23 Art. hypertension, % 6870 Diabetes, % 2829 Current smoker, % 1513 Hypercholesterolemia, % 6976

15. Resolute n=324 Xience n=326 Acute Coronary Syndrome, % 3833 History of MI, % 3229 Prior PCI, % 5254 Creatinine serum level, mg/dl 1.09 ±0.71 1.09 ±0.70 Parsonnet Score13.3 ±10.3 13.7 ±11.0 EuroSCORE5.1 ±3.7 5.0 ±3.7 Malignancies, %2224 Baseline Characteristics

16. Resolute n=324 Xience n=326 LV ejection fraction, % 52.1 ±11.9 53.8 ±11.4 Coronary artery dominance right left balanced 84 10 6 84 9 7 RCA ≥50% stenosis, % 6974 Dominant RCA occlusion, % 911 R. intermedius >2.0 mm, % 16 Angiographic Characteristics

17. Resolute n=324 Xience n=326 Ostium Midshaft Distal % Left Main Area Lesion Location

18. Single stenting Culotte stenting T-stenting Crush stenting % Stenting Technique Resolute n=324 Xience n=326

19. Definite stent thrombosis Probable stent thrombosis % Incidence of Stent Thrombosis - secondary endpoint - Resolute n=324 Xience n=326

20. 0 20 40 60 80 100 0123456789101112 Months after randomization Cumulative incidence, % Major Adverse Cardiac Events - primary endpoint - RR 1.26 (95% CI 0.85-1.85) P=.25 17.5% 14.3% Resolute Xience

21. 0 20 40 60 80 100 0123456789101112 Months after randomization Cumulative incidence, % Death or Myocardial Infarction RR 1.28 (95% CI 0.70-2.34) P=.42 7.5% 5.9% Resolute Xience

22. 0 20 40 60 80 100 0123456789101112 Months after randomization Cumulative incidence, % Death or Myocardial Infarction or Stroke RR 1.26 (95% CI 0.71-2.23) P=.43 8.1% 6.5% Resolute Xience

23. 0 20 40 60 80 100 0123456789101112 Months after randomization Cumulative incidence, % All-Cause Mortality RR 1.01 (95% CI 0.52-1.94) P=.98 5.6% Resolute Xience

24. % LMCA Area Restenosis Angiographic restenosis Clinical restenosis P=.20 P=.35 Resolute Xience

25. Target Lesion Revascularization % Resolute Xience TLR Repeat PCIBypass surgery RR 1.26 (95% CI 0.78-2.06) P=.35

26. MACE in Different Subgroups EuroSCORE ≥6 <6 Diabetes Yes No Parsonnet score >15 ≤15 No. of Events/Total (%) ResoluteXience 20/93 (21.9)24/92 (26.2) 26/233 (11.3)32/232 (14.0) 28/120 (23.7)24/115 (21.0) 28/204 (13.9)22/211 (10.6) 29/140 (20.7)23/120 (19.5) 27/184 (15.0)23/206 (11.3) P Value for Interaction 0.96 0.68 0.52 SubgroupRelative Risk (95% CI) Xience betterResolute better 030.511.522.5

27. The use of 2 nd gen. DES in unprotected LMCA lesions in relatively unselected patients is safe and effective. Both Endeavor Resolute and Xience stents provide similar clinical and angiographic outcomes at one-year follow-up in this high risk patient population. Summary