EXCEL vs. NOBLE: How to Treat Left Main Disease in 2017 AATS International Cardiovascular Symposium December 8-9, 2017

EXCEL vs. NOBLE: How to Treat Left Main Disease in 2017 AATS International Cardiovascular Symposium December 8-9, 2017 Igor F. Palacios, MD Director of Interventional Cardiology Professor of Medicine Massachusetts General Hospital Harvard Medical School

Main Left PCI vs. CABG Unprotected left main coronary artery (ulmca) disease has major prognostic implications and remains a therapeutic challenge. Current clinical practice guidelines from both sides of the Atlantic provide a Class I recommendation (Level of Evidence: A) for CABG) in these patients. Furthermore, these guidelines state that PCI have a Class III indication for ulmca patients otherwise eligible for surgery. A recent consensus document also indicates that PCI is inappropriate for ulmca.

PCI (1 st gen DES) vs. CABG for Left Main Ds. Meta-analysis of 4 RCTs, 1,611 Patients Trial LEMANS SYNTAX LM Boudriot et al. PRECOMBAT Year 2008 2009 2010 2011 N total 105 705 201 600 Age, mean years 61 65 68 62 Male 67% 74% 75% 77% Diabetes 18% 25% 36% 32% Distal LM involved 58% 61% 71% 65% +0/1/2/3 VD, % 0/9/23/68 13/20/31/36 29/31/27/14 10/17/32/41 Syntax Score, mean 25 30 24 25 Log Euroscore, mean 3.4 3.9 2.5 2.7 LIMA-LAD 81% 97% 99% 94% Capodanno D et al. JACC 2011;58:1426-32

PCI CABG OR (95%CI) OR (95%CI) p-value Death 3.0% 4.1% 0.74 (0.43-1.28) 0.29 (24/807) (32/790) MI 2.8% 2.9% 0.98 (0.54-1.78) 0.95 (23/807) (23/790) Stroke 0.1% 1.7% 0.15 (0.03-0.67) 0.01 (1/707) (12/689) Death, MI, or stroke 5.3% 6.8% 0.77 (0.48-1.22) 0.26 (35/655) (43/636) Repeat Revasc 11.4% 5.4% 2.25 (1.54-3.28) <0.001 (92/807) (43/790) MACCE 14.5% 11.8% 1.28 (0.95-1.72) 0.11 (117/807) (93/790) 0.01 0.1 1 10 100 Favors PCI Favors CABG Capodanno D et al. JACC 2011;58:1426-32

MACCE to 5 Years Left Main Subset CABG (N=348) TAXUS (N=357) Cumulative Event Rate (%) 50 25 0 Before 1 year * 13.7% vs 15.8% P=0.44 1-2 years * 7.5% vs 10.3% P=0.22 2-3 years * 5.2% vs 5.7% P=0.78 P=0.12 3-4 years * 6.4% vs 8.3% P=0.35 4-5 years * 5.9% vs 5.5% P=0.82 36.9% 31.0% 0 12 24 36 48 60 Months Since Allocation Cumulative KM Event Rate ± 1.5 SE log-rank P value; * Binary rates Serruys PW et al. Lancet 2013;381:629 38

MACCE to 12-Months vs. SYNTAX Score CABG (N=897) TAXUS Express Stent (N=903) 30 P=0.38 P=0.007 12-month MACCE, % 25 20 15 10 5 0 14.7 22 12.0 10.9 23-32 33 30 25 20 15 10 5 0 13.6 P=0.29 16.7 P=0.002 22 23-32 P=0.04 23.4 33 Serruys PW et al. Lancet 2013;381:629 38 SYNTAX Score

MACCE to 5 Years by SYNTAX Score Tercile LM Subset Low to Intermediate Scores (0-32) CABG (N=196) TAXUS (N=221) CABG PCI P value Cumulative Event Rate (%) 50 25 P=0.74 LM Disease 32.1% 31.3% Death 15.1% 7.9% 0.02 CVA 3.9% 1.4% 0.11 MI 3.8% 6.1% 0.33 Death, CVA or MI 19.8% 14.8% 0.16 0 0 12 24 36 48 60 Months Since Allocation Revasc. 18.6% 22.6% 0.36 Serruys PW et al. Lancet 2013;381:629 38

MACCE to 5 Years by SYNTAX Score Tercile LM Subset High Scores 33 CABG (N=149) TAXUS (N=135) CABG PCI P value 50 P=0.003 LM Disease 46.5% Death 14.1% 20.9% 0.11 CVA 4.9% 1.6% 0.13 MACCE (%) 25 29.7% MI 6.1% 11.7% 0.13 Death, CVA or MI 22.1% 26.1% 0.40 0 0 12 24 Months 36 48 60 Revasc. 11.6% 34.1% <0.001 Serruys PW et al. Lancet 2013;381:629 38

SYNTAX Score I vs II: The SYNTAX Trial Interactions: Diabetes Log HR P interaction = 0.67 PCI CABG Diabetes was not an independent predictor of mortality or MACE in either the CABG or PCI arm, and had a negative interaction effect No Yes Farooq V et al. Lancet 2013;381:639 50

Syntax I vs. Syntax II Scores The SYNTAX Score II was designed to improve decision making between CABG and PCI, by allowing for a long term, individualized risk assessment of patients with complex coronary artery disease. The SYNTAX Score II combines the anatomical based SYNTAX Score with clinical variables, that were shown to alter the threshold value of the SYNTAX Score so that equipoise was achieved between CABG and PCI for long term mortality. These variables included the presence of unprotected left main coronary artery disease, female gender, COPD, age and LVEF

SYNTAX: Definite/Probable ARC Stent Thrombosis to 5 Years (Per Patient) 12 12 10.4 ~4.5% ST in year 1 ~1.2% ST/yr in years 2-4 6 6 2.6 0.3 1.7 1.3 1.4 1.2 0.9 0 (3/896) (23/893) (15/874) (11/850) (12/830) Acute 1d Subacute 2-30d Late 31-365d Very Late 366-731- 1096-730d 1095d 1460d Days Post-procedure (10/803) (7/768) 1461-1825d 0 (76/730) Total 5 year Rate was ~ same in the LM and 3VD cohorts, and roughly independent of Syntax Score Farooq V et al. JACC 2013:62:2360 9

Is Everolimus-eluting stent superior to TAXUS eluting stent respect to longterm individual clinical outcomes? 1. This is a meta-analysis of the final 3-year results from the international SPIRIT II, III, and IV clinical trials. Individual patient data from 4,989 patients who were prospectively randomized to treatment with EES (n = 3,350) or PES (n = 1,639) were pooled for analysis. 2. In this large dataset with 3-year follow-up, coronary implantation of EES compared with PES resulted in reduced rates of all-cause mortality, myocardial infarction, ischemia-driven TLR, stent thrombosis, and TLF.

EES vs. TAXUS: SPIRIT II, III, IV and COMPARE RCTs. Patients with multivessel PCI (n=1,322) Xience V / Promus (n=790) At 3-year follow-up, Taxus (n=532) EES was superior to PES in reducing 17.4% Death, MI, or ischemia-driven TLR (%) 15 the following event rates: TLF (8.9% vs. 12.5%, hazard 11.8% p = 0.0002), all-cause mortality (3.2% vs 5.1%, HR: 0.65, HR: 0.64 [0.48, 0.85] 5 (4.4% vs. 6.3%, HR: 0.70, 95% CI: 0.54 to 0.90; p = 0.005), Xience V Taxus 20 ratio [HR]: 0.71, 95% confidence interval [CI]: 0.59 to 0.85; 10 95% CI: 0.49 to 0.86; p = 0.003), MI (3.2% vs. 5.1%, HR: 0.64, 95% CI: 0.48 to 0.85; p = 0.002), cardiac death or MI ischemia-driven TLR (6.0% vs. 8.2%, HR: 0.72, P=0.002 95% CI: 0.58 to 0.90; p = 0.004), stent thrombosis (0.7% vs. 1.7%, 0 HR: 0.45, 95% CI: 0.26 to 0.78; p = 0.003), and MACCE Stone GW. TCT 2012 0 3 6 9 12 15 18 21 24 No. (9.4% at riskvs. 13.0%, HR: 0.71, Time 95% in Months CI: 0.60 to 0.85; p = 0.0002). 790 532 752 478 720 451 969 430 624 387

Network Meta-analysis: 77 RCTs, 57,138 pts 1-year definite stent thrombosis Control BMS (Ref) Sirolimus (Ref) Paclitaxel (Ref) Everolimus (Ref) Zotarolimus (Ref) Treatment Sirolimus Paclitaxel Everolimus Zotarolimus Zotarolimus-R Paclitaxel Everolimus Zotarolimus Zotarolimus-R Everolimus Zotarolimus Zotarolimus-R Zotarolimus Zotarolimus-R Favors Treatment OR (95% Crl) Favors Control OR [95% CrI] 0.75 (0.45, 1.20) 0.81 (0.51, 1.48) 0.27 (0.14, 0.55) 1.34 (0.63, 3.21) 0.41 (0.41, 12.53) 1.10 (0.66, 1.91) 0.36 (0.20, 0.70) 1.79 (0.91, 4.04) 2.73 (0.60, 16.87) 0.34 (0.18, 0.61) 1.70 (0.76, 3.60) 2.52 (0.51, 14.79) 5.16 (2.09, 12.31) 7.44 (1.88, 39.43) Zotarolimus-R 1.55 (0.29, 9.83) 0.10 1.00 10.00 Bangalore S et al. Circulation 2012;125:2873-91

EXCEL Study Design 2900 pts with unprotected left main disease SYNTAX score 32 Consensus agreement of eligibility and equipoise by heart team Stratified by diabetes, SYNTAX score and center Yes (N=1900) R No (N=1000) Enrollment registry PCI (Xience EES) (N=950) CABG (N=950) Follow-up: 1 month, 6 months, 1 year, annually through 5 years Primary endpoint: Measured at a median 3-yr FU, minimum 2-yr FU

EXCEL Major Inclusion Criteria Unprotected LMCAD with 70% DS, or 50% - <70% with either I) non-invasive evidence of LM ischemia, II) IVUS MLA 6.0 mm 2, or III) FFR 0.80 Syntax score 32 Clinical and anatomic eligibility for both PCI and CABG as agreed to by the local Heart Team

EXCEL Major Exclusion Criteria Prior CABG or LM PCI anytime Prior non-lm PCI within 1 year Need for cardiac surgery other than CABG Inability to tolerate DAPT for 1 year CK-MB >ULN

EXCEL Primary and Secondary Endpoints Endpoint Timing of follow-up Powered for Primary endpoint: Death, stroke or MI Median 3 years, minimum 2 years Non-inferiority Secondary endpoint #1: Death, stroke or MI 30 days Non-inferiority Secondary endpoint #2a: Death, stroke, MI or IDR Secondary endpoint #2b: Death, stroke or MI Median 3 years, minimum 2 years Median 3 years, minimum 2 years Non-inferiority Superiority If the primary endpoint and secondary endpoint #1 both pass, secondary endpoints #2a and #2b are tested simultaneously IDR = ischemia-driven revascularization

EXCEL Enrollment 2905 patients enrolled at 126 sites in 17 countries Screening registry phase open Randomized enrollment N=747 Screening registry closed Randomized enrollment N=1158 additional N=1905 total randomized Registry enrollment N=1000 Followed through initial treatment (no outcomes data) N=1000 PCI with CoCr-EES N=948 CABG N=957

EXCEL Primary and Hierarchical Secondary Clinical Outcomes PCI (n=948) CABG (n=957) Diff [upper confidence limit] P NI HR [95%CI] P Sup Primary endpoint Death, stroke or MI at 3 years 15.4% 14.7% 0.7% [4.0%] 0.018 - - Secondary endpoints Death, stroke or MI at 30 days Death, stroke, MI or ischemia-driven revasc at 3 years Death, stroke or MI at 3 years 4.9% 7.9% -3.1% [-1.2%] <0.001 - - 23.1% 19.1% 4.0% [7.2%] 0.01 - - 15.4% 14.7% - - 1.00 [0.79, 1.26] 0.98 The pre-specified non-inferiority margins (deltas) were 4.2% for death, stroke or MI at 3 years, 2.0% for death, stroke or MI at 30 days, and 8.4% for death, stroke, MI or ischemia-driven revascularization at 3 years. Upper 97.5% confidence limit; Upper 95.0% confidence limit.

Primary and Hierarchical Secondary Clinical Outcomes PCI (n=948) CABG (n=957) Diff [upper confidence limit] P NI HR [95%CI] P Sup Primary endpoint Death, stroke or MI at 3 years 15.4% 14.7% 0.7% [4.0%] 0.018 - - Secondary endpoints Death, stroke or MI at 30 days Death, stroke, MI or ischemia-driven revasc at 3 years Death, stroke or MI at 3 years 4.9% 7.9% -3.1% [-1.2%] <0.001 - - 23.1% 19.1% 4.0% [7.2%] 0.01 - - 15.4% 14.7% - - 1.00 [0.79, 1.26] 0.98 The pre-specified non-inferiority margins (deltas) were 4.2% for death, stroke or MI at 3 years, 2.0% for death, stroke or MI at 30 days, and 8.4% for death, stroke, MI or ischemia-driven revascularization at 3 years. Upper 97.5% confidence limit; Upper 95.0% confidence limit.

EXCEL Primary and Hierarchical Secondary Clinical Outcomes PCI (n=948) CABG (n=957) Diff [upper confidence limit] P NI HR [95%CI] P Sup Primary endpoint Death, stroke or MI at 3 years 15.4% 14.7% 0.7% [4.0%] 0.018 - - Secondary endpoints Death, stroke or MI at 30 days Death, stroke, MI or ischemia-driven revasc at 3 years Death, stroke or MI at 3 years 4.9% 7.9% -3.1% [-1.2%] <0.001 - - 23.1% 19.1% 4.0% [7.2%] 0.01 - - 15.4% 14.7% - - 1.00 [0.79, 1.26] 0.98 The pre-specified non-inferiority margins (deltas) were 4.2% for death, stroke or MI at 3 years, 2.0% for death, stroke or MI at 30 days, and 8.4% for death, stroke, MI or ischemia-driven revascularization at 3 years. Upper 97.5% confidence limit; Upper 95.0% confidence limit.

EXCEL Primary and Hierarchical Secondary Clinical Outcomes PCI (n=948) CABG (n=957) Diff [upper confidence limit] P NI HR [95%CI] P Sup Primary endpoint Death, stroke or MI at 3 years 15.4% 14.7% 0.7% [4.0%] 0.018 - - Secondary endpoints Death, stroke or MI at 30 days Death, stroke, MI or ischemia-driven revasc at 3 years Death, stroke or MI at 3 years 4.9% 7.9% -3.1% [-1.2%] <0.001 - - 23.1% 19.1% 4.0% [7.2%] 0.01 - - 15.4% 14.7% - - 1.00 [0.79, 1.26] 0.98 The pre-specified non-inferiority margins (deltas) were 4.2% for death, stroke or MI at 3 years, 2.0% for death, stroke or MI at 30 days, and 8.4% for death, stroke, MI or ischemia-driven revascularization at 3 years. Upper 97.5% confidence limit; Upper 95.0% confidence limit.

EXCEL Primary and Hierarchical Secondary Clinical Outcomes Primary Endpoint PCI (n=948) CABG (n=957) Diff [upper confidence limit] P NI HR [95%CI] P Sup Death, stroke or MI at 3 years 15.4% 14.7% 0.7% [4.0%] 0.018 - - Secondary endpoints Death, stroke or MI at 30 days Death, stroke, MI or ischemia-driven revasc at 3 years Death, stroke or MI at 3 years 4.9% 7.9% -3.1% [-1.2%] <0.001 - - 23.1% 19.1% 4.0% [7.2%] 0.01 - - 15.4% 14.7% - - 1.00 [0.79, 1.26] 0.98 The pre-specified non-inferiority margins (deltas) were 4.2% for death, stroke or MI at 3 years, 2.0% for death, stroke or MI at 30 days, and 8.4% for death, stroke, MI or ischemia-driven revascularization at 3 years. Upper 97.5% confidence limit; Upper 95.0% confidence limit.

EXCEL Primary Endpoint Death, Stroke or MI at 3 Years Death, stroke or MI (%) 25% 20% 15% 10% 5% CABG (n=957) PCI (n=948) HR [95%CI] = 1.00 [95% CI: 0.79, 1.26] P = 0.98 15.4% 14.7% 0% No. at Risk: PCI CABG 0 1 6 12 24 36 Months 948 896 875 850 784 445 957 868 836 817 763 458

EXCEL Adjudicated Outcomes at 30 Days PCI (n=948) CABG (n=957) HR [95%CI] P-value Death, stroke or MI 4.9% 7.9% 0.61 [0.42, 0.88] 0.008 - Death 1.0% 1.1% 0.90 [0.37, 2.22] 0.82 - Stroke 0.6% 1.3% 0.50 [0.19, 1.33] 0.15 - MI 3.9% 6.2% 0.63 [0.42, 0.95] 0.02 - Peri-procedural 3.6% 5.9% 0.61 [0.40, 0.93] 0.02 - Spontaneous 0.3% 0.3% 1.00 [0.20, 4.95] 1.00 - STEMI 0.7% 2.3% 0.32 [0.14, 0.74] 0.005 - Non-STEMI 3.2% 3.9% 0.82 [0.50, 1.32] 0.41 Death, stroke, MI or IDR 4.9% 8.4% 0.57 [0.40, 0.82] 0.002 - Ischemia-driven revasc (IDR) 0.6% 1.4% 0.46 [0.18, 1.21] 0.11 Stent thrombosis, def/prob 0.6% 0.0% - 0.01 Graft occlusion, symptomatic 0.0% 1.2% - <0.001 Definite stent thrombosis or symptomatic graft occlusion 0.3% 1.2% 0.27 [0.08, 0.97] 0.03

EXCEL Adjudicated Outcomes at 3 Years (I) PCI (n=948) CABG (n=957) HR [95%CI] P-value Death, stroke or MI (1 endpoint) 15.4% 14.7% 1.00 [0.79, 1.26] 0.98 - Death 8.2% 5.9% 1.34 [0.94, 1.91] 0.11 - Definite cardiovascular 3.7% 3.4% 1.10 [0.67, 1.80] 0.71 - Definite non-cardiovascular 3.9% 2.3% 1.60 [0.91, 2.80] 0.10 - Undetermined cause 0.8% 0.3% 2.00 [0.50, 7.98] 0.32 - Stroke 2.3% 2.9% 0.77 [0.43, 1.37] 0.37 - MI 8.0% 8.3% 0.93 [0.67, 1.28] 0.64 - Peri-procedural 3.8% 6.0% 0.63 [0.42, 0.96] 0.03 - Spontaneous 4.3% 2.7% 1.60 [0.95, 2.70] 0.07 - STEMI 1.3% 2.8% 0.46 [0.23, 0.91] 0.02 - Non-STEMI 7.0% 5.9% 1.15 [0.80, 1.65] 0.46

EXCEL Primary Endpoint Landmark Analysis (post hoc) From randomization to 30 days From 30 days to 3 years PCI (n=948) CABG (n=957) HR [95%CI] P value PCI (n=939) CABG (n=947) HR [95%CI] P valu Death, stroke or MI 4.9% 7.9% 0.61 [0.42, 0.88] 0.008 11.5% 7.9% 1.44 [1.06, 1.96] 0.02 - Death 1.0% 1.1% 0.90 [0.37, 2.22] 0.82 7.3% 4.9% 1.44 [0.98, 2.13] 0.06 - Stroke 0.6% 1.3% 0.50 [0.19, 1.33] 0.15 1.8% 1.8% 1.00 [0.49, 2.05] 1.00 - MI 3.9% 6.2% 0.63 [0.42, 0.95] 0.02 4.2% 2.5% 1.71 [1.00, 2.93] 0.05 Stroke and MI rates are non-hierarchical; i.e. include fatal and non-fatal events. The 30-day to 3-year landmark period includes all randomized pts at day 30 except those who died before day 30. Thus there may be some patients with a stroke or MI within 30 days who have a second event between 30 days and 3 years.

EXCEL 3-Year Death, Stroke or MI Subgroup PCI (N=948) CABG (N=957) HR [95% CI] Favors PCI Favors CABG P (Int) All patients 15.4% 14.7% 1.00 [0.79, 1.26] Age (median cutoff) - 67 years 18.7% 15.0% 1.22 [0.89, 1.69] - <67 years 12.2% 14.4% 0.78 [0.55, 1.11] 0.07 Gender - Male 14.0% 14.9% 0.87 [0.66, 1.14] - Female 19.7% 14.1% 1.48 [0.93, 2.41] 0.06 Diabetes mellitus - Yes 21.2% 19.4% 1.04 [0.70, 1.55] - No 13.3% 13.1% 0.97 [0.72, 1.30] 0.77 Chronic kidney disease - egfr 60 ml/min 24.5% 19.3% 1.24 [0.75, 2.07] - egfr >60 ml/min 13.5% 13.6% 0.95 [0.72, 1.25] 0.36 Geographic location - North America 15.5% 12.4% 1.22 [0.82, 1.82] - Europe 15.5% 15.6% 0.95 [0.69, 1.29] - Other 9.5% 22.2% 0.37 [0.08, 1.20] 0.14 0.1 0.5 0.8 1 1.5 2 5 Hazard Ratio [95% CI]

EXCEL 3-Year Death, Stroke or MI Subgroup PCI (N=948) CABG (N=957) HR [95% CI] Favors PCI Favors CABG P (Int) All patients 15.4% 14.7% 1.00 [0.79, 1.26] Left ventricular ejection fraction - 50% 14.7% 14.4% 0.98 [0.75, 1.27] - <50% 20.4% 18.2% 0.98 [0.52, 1.83] Non-LM diseased coronary arteries - 0 14.6% 14.4% 0.99 [0.54, 1.79] - 1 12.3% 16.0% 0.72 [0.46, 1.12] - 2 18.8% 12.7% 1.44 [0.96, 2.21] - 3 15.2% 16.8% 0.87 [0.50, 1.48] LM bifurcation or trifurcation stenosis 50% - Yes 15.6% 15.3% 0.98 [0.75, 1.27] - No 14.8% 12.9% 1.05 [0.59, 1.87] Syntax score (site reported) - 22 14.3% 14.4% 0.95 [0.70, 1.31] - 23-32 17.0% 15.4% 1.05 [0.73, 1.51] Syntax score (core lab assessment) - 22 10.3% 13.3% 0.71 [0.44, 1.13] - 23-32 17.6% 16.5% 1.02 [0.71, 1.47] - 33 16.9% 14.3% 1.15 [0.71, 1.87] 0.99 0.78 0.82 0.70 0.49 0.1 0.5 0.8 1 1.5 2 5 Hazard Ratio [95% CI]

NOBLE - Design A prospective, randomized, open-label, noninferiority trial, carried out at 36 hospitals in Latvia, Estonia, Lithuania, Germany, Norway, Sweden, Finland, United Kingdom, and Denmark Enrollment: December 2008 to January 2015

NOBLE Inclusion criteria Stable angina, UAP, or ACS A significant left main lesion: Visually assessed stenosis diameter >50% or fractional flow reserve 0.80. Located in the ostium, mid-shaft, or bifurcation No more than three additional non-complex lesions Interventional cardiologists and cardiac surgeons determined that equivalent revascularization could be achieved with CABG or PCI

NOBLE Exclusion criteria Additional non left main complex lesions Chronic total occlusions Bifurcation lesions requiring two stent techniques Calcified or tortuous vessel morphology ST-elevation infarction within 24 h Being considered too high-risk for CABG or PCI Expected survival of less than 1 year

NOBLE Primary endpoint A composite of major adverse cardiac and cerebrovascular events (MACCE) Death from any cause Non-procedural myocardial infarction Repeat revascularization Stroke

NOBLE Secondary Endpoints The individual components of the primary endpoint Definite stent thrombosis Symptomatic graft occlusion Procedural myocardial infarction (post hoc) Repeat revascularization Target lesion Left main coronary artery target lesion De novo lesion

NOBLE Primary Endpoint * HR 1 48 (1 11 1 96); p=0 0066 28 9% 19 1% PCI did not show non-inferiority and CABG was superior to PCI * MACCE (death from any cause, non-procedural MI, repeat revascularization, stroke)

NOBLE All-cause Mortality HR 1 07 (0 67 1 72); p=0 77 11 6% 9 5%

NOBLE Non-procedural MI HR 2 88 (1 40 5 90); p=0 004 6 9% 1 9%

NOBLE Total Repeat Revascularization HR 1 50 (1 04 2 17); p=0 03 16 2% 10 4%

NOBLE - Stroke HR 2 25 (0 92 5 48); p=0 07 4 9% 1 7%

NOBLE and Syntax Score Subgroups K-M estimates 4.9% 1.9% HR 1 88 (1 23 2 89); p=0 0031 HR 1 16 (0 76 1 78); p=0 48 HR 1 41 (0 62 3 20); p=0 41 SYNTAX score assessed by independent core lab (CERC)

Randomized LM PCI vs. CABG trials N patients, sites NOBLE 1,200 @ 26 EU sites EXCEL 1,900 @ 126 sites in 17 countries DES Biomatrix BES recommended Xience EES LM location Ostial, shaft, or bifurcation Ostial, shaft, or bifurcation LM severity Angio DS >50% or FFR 0.80 Other anatomic inclusion criteria 3 additional non-complex lesions (excludes length >25 mm, CTO, 2-stent bifurcation, calcified or tortuous vessels) Angio DS 70% or 50% - <70% + either FFR 0.80 or IVUS MLA 6.0 mm 2 or non-invasive evidence of extensive ischemia Syntax Score 32 Primary endpoint D, CVA, non-index MI, revasc D, CVA, MI Timing of primary EP 2 years Median 3 years Duration of follow-up 5 years 5 years

Conclusions Whether PCI is non-inferior or superior to CABG in pts with LM disease and mild and moderate anatomic complexity was not answered by the EXCEL and NOBLE trials. Treatment of patients with LMCAD and low or intermediate SYNTAX scores with CoCr-EES resulted in similar rates of the primary endpoint of death, stroke or MI at 3 years, with fewer adverse events within 30 days compared to CABG. PCI may thus be considered an acceptable or even preferred revascularization modality for selected patients with LMCAD, a decision which should be made after heart team discussion, taking into account each patient s