SYNTAX at 2 Years: This Interventionalist’s Perspective David J. Cohen, M.D., M.Sc. Director of Cardiovascular Research Saint Luke’s Mid America Heart Institute Professor of Medicine University of Missouri-Kansas City

I am a practicing interventional cardiologist DISCLOSURES David J. Cohen, MD Consulting Fees Medtronic CardioVascular, Inc., Cordis, a Johnson & Johnson company Grants/Contracted Research Abbott Vascular, Boston Scientific Corporation, Daiichi Sankyo, Inc. and Eli Lilly and Company, Edwards Lifesciences LLC I am a practicing interventional cardiologist I have many friends who are cardiac surgeons (and a couple of them are actually pretty smart!)

SYNTAX Trial: Design 1800 patients with 3-vessel or left main CAD, considered to be suitable for both PCI and CABG by both an interventional cardiologist and CT surgeon Randomized to PCI with TAXUS DES (n=903) or CABG (n=897) Primary endpoint = Death, MI, Stroke, or repeat revacularization (MACCE) at 1 year Parallel registries of patients felt to be only suitable for either PCI (n=198) or CABG (n=1077), but not both

2-Year MACCE SYNTAX P<0.001 20 40 Cumulative Event Rate (%) 23.4% Before 1 year* 12.4% vs 17.8% P=0.002 After 1 year* 5.7% vs 8.3% P=0.03 Cumulative Event Rate (%) 23.4% 16.3% 12 24 Months Since Allocation Kappetein P et al. ESC 2009 4

All-Cause Death/CVA/MI to 2 Years TAXUS (N=903) CABG (N=897) P=0.44 20 40 Before 1 year* 7.7% vs 7.6% P=0.98 After 1 year* 2.2% vs 3.5% P=0.11 Cumulative Event Rate (%) 1 yr data From SYNTAX_CSR_randomized_Unblinded_2008Oct10.doc exhibit 1 2-Year_Randomized_20090820.doc Exhibits 1&2 compare curves to Exhibit 9 10.8% 9.6% 12 24 Months Since Allocation Cumulative KM Event Rate ± 1.5 SE; log-rank P value;*Binary rates ITT population 5

Repeat Revascularization to 2 Years TAXUS (N=903) CABG (N=897) P<0.001 20 40 Before 1 year* 5.9% vs 13.5% P<0.001 After 1 year* 3.7% vs 5.6% P=0.06 Cumulative Event Rate (%) 17.4% 1 yr data From SYNTAX_CSR_randomized_Unblinded_2008Oct10.doc exhibit 1 2-Year_Randomized_20090820.doc Exhibits 1&2 compare curves to Exhibit 15 8.6% 12 24 Months Since Allocation Cumulative KM Event Rate ± 1.5 SE; log-rank P value;*Binary rates ITT population 6

SYNTAX in Perspective: Quality of Life Since there is no significant difference in mortality at 2 years, the next most important outcome from a patient’s perspective is symptoms and quality of life

Primary QOL Endpoint: SAQ-Angina Frequency PCI Benefit vs. OMT in COURAGE 6 points @ 6 months 3 points @ 12 months

Generic QOL and Utilities 30 35 40 45 50 55 Baseline 1 month 6 months 12 months P<0.001 P=0.50 P=0.07 SF - 36 Physical Component Summary 30 40 50 Baseline 1 month 6 months 12 months SF - 36 Mental Component Summary P<0.001 P=0.23 P=0.43 0.5 0.6 0.7 0.8 0.9 1 Baseline 1 month 6 months 12 months P<0.001 P=0.16 P=0.99 EQ - 5D Utilities (US) PCI CABG Quality Adjusted Life Years D = 0.02 (P<0.01)

SYNTAX in Perspective: Subgroups

2 Year Outcomes in 3VD and LM Subgroups TAXUS CABG P=0.11 P<0.001 P<0.001 P=0.48 P=0.01 P=0.27 Patients, % Patients, % 2-Year_Randomized_20090820.doc Exhibits 19 & 21 Death/CVA/MI Revasc MACCE Death/CVA/MI Revasc MACCE 3 Vessel Disease n=1095 Left Main Disease n=705 Time-to Event; Log-rank P value ITT population

2-Year MACCE: SYNTAX Score Tertiles P<0.001 P=NS P=NS P = 0.001 for interaction Low (≤22) Middle 23-32 High (≥33) CABG PCI

Cost-Effectiveness of CABG vs. PCI ($/QALY) SYNTAX Score Tertiles Dominated ICER -0.047 D QALY $6154 D Cost Low (≤22) Pr <$50K/QALY = 0.0% Dominated ICER -0.013 D QALY $3889 D Cost Mid (23-32) Pr <$50K/QALY = 0.3% $43,000/QALY ICER +0.010 D QALY $467 D Cost High (≥33) Pr <$50K/QALY = 49%

SYNTAX at 2 Years Dirty Little Secrets CABG results representative of current US practice Although it’s possible that greater use of bilateral IMAs would have resulted in better outcomes, there are currently no RCT data to support this assertion This would also require a substantial change from current standard of care PCI results could definitely have been better TAXUS recently shown to be inferior to Xience V for both TVR and MI outcomes FAME suggests that better results could have been achieved with fewer stents by using physiologic guidance

SYNTAX at 2 Years What have we learned? Some patients are uniquely suited to PCI or CABG due to comorbid conditions or technical issues Most patients with multivessel disease will have a choice For these patients, the decision is largely based on one’s preference to either avoid bypass surgery (and the prolonged recovery period) or to avoid the need for additional procedures in the short-to-intermediate term

What else have we learned? SYNTAX at 2 Years What else have we learned? The SYNTAX score may be a helpful tool to better inform patients and their physicians about the relative benefits of PCI and CABG– particularly in complex 3-vessel disease (where CABG is the clear winner) If the SYNTAX results can be replicated, left main disease (especially isolated LM) may be a highly attractive subset for PCI in the future