E. Boudriot*, H.Thiele*, T.Walther, C.Liebetrau, P.Boeckstegers, T.Pohl, B.Reichart, H.Mudra, F.Beier, B. Gansera, F.J.N

1. Randomized Comparison of Percutaneous Coronary Intervention with Sirolimus-Eluting Stents versus Coronary Artery Bypass Grafting in Unprotected Left Main Stem Stenosis E. Boudriot*, H.Thiele*, T.Walther, C.Liebetrau, P.Boeckstegers, T.Pohl, B.Reichart, H.Mudra, F.Beier, B. Gansera, F.J.Neumann, M.Gick, T. Zietak, S. Desch, G.Schuler, F.W.Mohr * Both authors contributed equally Disclosures: supported in part by Deutsche Stiftung für Herzforschung

2. Study Prospective randomized trial CABG(arterial grafts)versus PCI + Sirolimus-Eluting Stentin left main stem stenosis • Primary combined endpoint within 12 months • Mortality • Myocardial infarction • Target vessel revascularization (TVR) • Secondary endpoints • Individual clinical endpoints • Periinterventional complications • CCS-classification • low output syndrome (intravenous catecholamines and/or IABP) • Congestive heart failure requiring hospital admission • cerebrovascular events (stroke, coma, TIA, PRIND) • pericardial tamponade • arrhythmia (ventricular fibrillation, VT, A. fibrillation) • major bleeding requiring blood transfusion • re-thoracotomy for bleeding • renal failure requiring dialysis • major infections compromising post-procedural rehabilitation • vascular access site complications requiring surgery • Sternum instability requiring additional treatment

3. Study Centers Universität München - Großhadern Klinikum Neuperlach München Herzzentrum Bad Krozingen Herzzentrum Leipzig

4. Statistics – Sample Size Inferior Inferior Zone of non-inferiority Limit of equivalence (10.0%) 90% CI -10.0 0 5.0 -15.0 -5.0 10.0 15.0 Stenting better CABG better Difference in MACE rates Assumed event rates: CABG: 15%, DES: 12.5% Difference in MACE rates of 2.5%  2 x 100 patients to show non-inferiority

5. Study Flow Chart 430 Patients with Unprotected Left Main Disease 229 Non-Eligible 22 Infarction < 48 Hours 11 Cardiogenic Shock 8 Chronic Total Occlusion 65 Lesion Length > 30 mm 6 Non-CABG Suitable 14 Prior Cardiac Surgery 36 Age > 80 Years 21 Malignancy 27 Combined Cardiac Surgery 19 Dominant Left Circumflex 179 CABG 201 Eligible 40 PCI 100 Assigned to PCI 101 Assigned to CABG 10 Conservative 3 Converted to CABG 5 No Angiographic Follow-up 20 No Angiographic Follow-up 1 Lost to Follow-up 0 Lost to Follow-up 100 Included in Primary Analysis 100 Included in Secondary Analysis 100 Included in Primary Analysis 100 Included in Secondary Analysis

6. Patient Characteristics

7. Angiographic Characteristics

8. Type of Left Main Stenosis PCI CABG 23% Ostium 20% 8% 6% Body 70% 74% Distal p = 0.72

9. Any complication 4 (4%) 30 (30%) <0.001 Periinterventional Complications Stenting CABGp (n=100)(n=101) Major bleeding- 2 (2%) CV accident -2 (2%) A. fibrillation 3 (3%) 19 (19%) Access site complication - -- Re-thoracotomy- 2 (2%) Major infection-5 (5%) Renal failure + dialysis 1 (1%) 1 (1%) Critical illness PNP - 1 (1%) CHF with readmission - - Pericardial tamponade - -

10. p=0.67 p=0.19 p<0.001 p<0.001 0.0 (IQR 0.0;1.0) 0.0 (IQR 0.0;1.0) 12 Months Change in CCS-Classification 3 2.5 3.0 (IQR 2.0;4.0) 2 PCI CCS-Class 1.5 CABG 2.0 (IQR 2.0;4.0) 1 0.5 0 Baseline

11. Primary Endpoint – MACE 12 Months PCICABG 95% CI p-Value (n=100) (n=101) Non-inferiority Death 2 (2.0%) 5 (5.0%) -8.2 to 2.9 <0.001 AMI 3 (3.0%) 3 (3.0%) -5.8 to 5.9 0.002 <30 days 3 (3.0%) 3 (3.0%) -5.8 to 5.9 0.002 day 30-12 m. - - Death + AMI 5 (5.0%) 8 (7.9%) -10.6 to 4.4 <0.001 Repeat revasc. 14 (14.0%) 6 (5.9%) -0.3 to 17.1 0.35 <30 days 1 (1.0%) 2 (2.0%) -6.1 to 3.7 <0.001 day 30-12 m. 13 (13.0%) 4 (4.0%) -1.3 to 17.6 0.45 Any MACE 19 (19.0%) 14 (13.9%) -5.3 to 15.7 0.19

12. MACE 12 Month p value for non-inferiority p = 0.19 p = 0.35 p < 0.001 p = 0.02

13. Primary Endpoint – MACE 12 Months Intention to treat Limit of equivalence -9.4 -3.0 2.7 <0.001 Death 5.9 0 -5.8 0.002 AMI 17.1 -0.3 8.1 Repeat revascularization 0.35 5.1 -5.3 15.7 0.19 MACE 0 5.0 -15.0 -5.0 -10.0 10.0 15.0 PCI better CABG better

14. CABG PCI Log-rank: p = 0.13 MACE Mid-term Follow-up Median follow-up 36.5 months 100 80 60 Cumulative major adverse cardiac event free survival (%) 40 20 0 1200 600 900 1500 1800 300 Days after randomization

15. Death and MI – Mid-term Follow-up PCI CABG Log-rank: p = 0.97 Median follow-up 36.5 months 100 80 60 Cumulative death and MI event free survival (%) 40 20 0 1200 600 900 1500 1800 300 Days after randomization

16. CABG PCI Log-rank: p = 0.03 TVR - Mid-term Follow-up Median follow-up 36.5 months 100 80 60 Cumulative major adverse cardiac event free survival (%) 40 20 0 1200 600 900 1500 1800 300 Days after randomization

17. Summary • In patients with unprotected left main stenosis • PCI using DES failed to show non-inferiority to CABG. • The inferiority for PCI is driven by the higher repeat revascularization rate. • For death and MI the results in both groups • are comparable. • Both treatment strategies effectively reduce symptoms.

18. Conclusions • In highly-experienced centers the decision making process on how to treat unprotected left main disease should therefore be based on an interdisciplinary approach taking into account the • - individual success, • - periprocedural risk • bypass graft occlusion risk • - potential restenosis rate • based on the morphology of the underlying lesion and patient comorbidities.