UNIVERSITÄT LEIPZIG H E R Z Z E N T R U M 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 Disclosures: supported in part by Deutsche Stiftung für Herzforschung * Both authors contributed equally

UNIVERSITÄT LEIPZIG H E R Z Z E N T R U M Study Primary combined endpoint within 12 months - Mortality - Myocardial infarction - Target vessel revascularization (TVR)  Secondary endpoints - Individual clinical endpoints - Periinterventional complications - CCS-classification Prospective randomized trial CABG (arterial grafts) versus PCI + Sirolimus-Eluting Stent in left main stem stenosis 1)low output syndrome (intravenous catecholamines and/or IABP) 2)Congestive heart failure requiring hospital admission 3)cerebrovascular events (stroke, coma, TIA, PRIND) 4)pericardial tamponade 5)arrhythmia (ventricular fibrillation, VT, A. fibrillation) 6)major bleeding requiring blood transfusion 7)re-thoracotomy for bleeding 8)renal failure requiring dialysis 9)major infections compromising post-procedural rehabilitation 10)vascular access site complications requiring surgery 11)Sternum instability requiring additional treatment

UNIVERSITÄT LEIPZIG H E R Z Z E N T R U M Study Centers Universität München - Großhadern Klinikum Neuperlach München Herzzentrum Bad Krozingen Herzzentrum Leipzig

UNIVERSITÄT LEIPZIG H E R Z Z E N T R U M Statistics – Sample Size Zone of non-inferiority Limit of equivalence (10.0%) 90% CI Stenting better CABG better Difference in MACE rates Inferior Assumed event rates: CABG: 15%, DES: 12.5% Difference in MACE rates of 2.5%  2 x 100 patients to show non-inferiority

UNIVERSITÄT LEIPZIG H E R Z Z E N T R U M Study Flow Chart 201 Eligible 100 Assigned to PCI101 Assigned to CABG 100 Included in Primary Analysis 100 Included in Secondary Analysis 0 Lost to Follow-up 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 1 Lost to Follow-up 100 Included in Primary Analysis 100 Included in Secondary Analysis 40 PCI 179 CABG 10 Conservative 5 No Angiographic Follow-up 20 No Angiographic Follow-up 3 Converted to CABG

UNIVERSITÄT LEIPZIG H E R Z Z E N T R U M Patient Characteristics Variable PCI * (n=100) CABG (n=101) P Value Age (y), median (IQR) 66 (62;73)69 (63;73) 0.24 Men, No. (%) 72 (72)78 (77) 0.49 Body-mass-index (kg/m 2 ), median (IQR) 27.2 (24.6;31.5)27.0 (24.9;30.1) 0.31 Cardiovascular risk factors, No. (%) Current smoking, No. (%) Hypertension, No. (%) Hypercholesterolemia, No. (%) Diabetes mellitus, No. (%) 35 (35) 82 (82) 68 (68) 40 (40) 28 (28) 83 (82) 65 (64) 33 (33) Previous myocardial infarction, No. (%) Q wave infarction, No. (%) Non-Q wave infarction, No. (%) 19 (19) 17 (17) 2 (2) 14 (14) 10 (10) 4 (4) 0.43 Previous stroke, No. (%) 3 (3)6 (6) 0.51 Baseline creatinine, median (IQR),  mol/l 86.0 (76.5;100.0)86.0 (75.0;97.0) 0.52 Left ventricular ejection fraction (%), median (IQR) 65.0 (55.0;70.0)65.0 (55.0;68.0) 0.88 Logistic EuroSCORE, median (IQR) 2.4 (1.5;3.7)2.6 (1.7;4.9) 0.08 Discharge medication, No. (%) Aspirin, No. (%) Clopidogrel, No. (%) Beta-blocker, No. (%) ACE-inhibitor‡/AT-1-ant.§, No. (%) Statins, No. (%) 100 (100) 99 (99) 98 (98) 97 (97) 101 (100) 32 (32) 96 (95) 93 (92) 95 (94) 0.99 <

UNIVERSITÄT LEIPZIG H E R Z Z E N T R U M Angiographic Characteristics VariablePCI (n=100) CABG (n=101) P Value Lesion type, No. (%) Ostial, No. (%) Trunk, No. (%) Distal, No. (%) 20 (20) 6 (6) 74 (74) 23 (23) 8 (8) 70 (69) 0.72 Isolated left main, No. (%) Left main + 1-vessel disease, No. (%) Left main + 2-vessel disease, No. (%) Left main + 3-vessel disease, No. (%) 28 (28) 35 (35) 26 (26) 11 (11) 29 (29) 27 (27) 28 (28) 17 (17) 0.49 PCI technique for distal left main T-Stenting, No. (%) Provisional T-stenting, No. (%) Crush-Stenting, No. (%) V-Stenting, No. (%) 40 (40) 30 (30) 3 (3) 1 (1) CABG, conduits per patient Left internal mammary artery, No. (%) Right internal mammary artery, No. (%) Radial artery, No. (%) Venous graft, No. (%) (99) 55 (54) 37 (37) 35 (35) SYNTAX score, median (IQR) 24.0 (19.0;29.0)23.0 (14.8;28.0)0.09

UNIVERSITÄT LEIPZIG H E R Z Z E N T R U M Ostium Body Distal PCI 20% 6% 74% CABG 23% 8% 70% Type of Left Main Stenosis p = 0.72

UNIVERSITÄT LEIPZIG H E R Z Z E N T R U M Stenting CABGp (n=100) (n=101) Major bleeding-2 (2%) CV accident-2 (2%) A. fibrillation3 (3%)19 (19%) Access site complication - -- Re-thoracotomy-2 (2%) Major infection-5 (5%) Renal failure + dialysis1 (1%)1 (1%) Critical illness PNP-1 (1%) CHF with readmission-- Pericardial tamponade-- Periinterventional Complications Any complication4 (4%)30 (30%)<0.001

UNIVERSITÄT LEIPZIG H E R Z Z E N T R U M Change in CCS-Classification Baseline PCI CABG CCS-Class p=0.19 p< (IQR 2.0;4.0) 2.0 (IQR 2.0;4.0) 12 Months p= (IQR 0.0;1.0)

UNIVERSITÄT LEIPZIG H E R Z Z E N T R U M PCICABG95% CI p-Value (n=100) (n=101) Non-inferiority Death2 (2.0%)5 (5.0%) -8.2 to 2.9 <0.001 AMI 3 (3.0%)3 (3.0%)-5.8 to <30 days3 (3.0%)3 (3.0%)-5.8 to day m.-- Death + AMI5 (5.0%)8 (7.9%)-10.6 to 4.4 <0.001 Repeat revasc.14 (14.0%)6 (5.9%)-0.3 to <30 days 1 (1.0%) 2 (2.0%)-6.1 to 3.7 <0.001 day m.13 (13.0%) 4 (4.0%)-1.3 to Any MACE19 (19.0%)14 (13.9%)-5.3 to Primary Endpoint – MACE 12 Months

UNIVERSITÄT LEIPZIG H E R Z Z E N T R U M MACE 12 Month p < p = 0.02 p = 0.35 p = 0.19 p value for non-inferiority

UNIVERSITÄT LEIPZIG H E R Z Z E N T R U M Primary Endpoint – MACE 12 Months Limit of equivalence PCI better CABG better AMI Repeat revascularization MACE Intention to treat Death <0.001

UNIVERSITÄT LEIPZIG H E R Z Z E N T R U M Days after randomization Cumulative major adverse cardiac event free survival (%) MACE Mid-term Follow-up Median follow-up 36.5 months CABG Log-rank: p = 0.13 PCI

UNIVERSITÄT LEIPZIG H E R Z Z E N T R U M Death and MI – Mid-term Follow-up Days after randomization Cumulative death and MI event free survival (%) Median follow-up 36.5 months Log-rank: p = 0.97 PCI CABG

UNIVERSITÄT LEIPZIG H E R Z Z E N T R U M TVR - Mid-term Follow-up Days after randomization Cumulative major adverse cardiac event free survival (%) Median follow-up 36.5 months CABG Log-rank: p = 0.03 PCI

UNIVERSITÄT LEIPZIG H E R Z Z E N T R U M 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. Summary

UNIVERSITÄT LEIPZIG H E R Z Z E N T R U M 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. Conclusions