Final Five-Year Follow-up of the SYNTAX Trial: Optimal Revascularization Strategy in Patients With Three-Vessel Disease and/or Left Main Disease Patrick W. Serruys, MD, PhD Thorax Centre, Erasmus MC On behalf of the SYNTAX investigators 9:06-16 a.m., Oct 22, 2012 Hall A, Coronary theater Conflicts of Interest: None 1

I, P. W. Serruys, DO NOT have a financial interest/arrangement or affiliation with one or more organizations that could be perceived as a real or apparent conflict of interest in the context of the subject of this presentation.

Study Design & Patient Disposition 62 EU Sites + 23 US Sites De novo 3VD and/or LM (isolated, +1,2,3 VD) Heart Team (Surgeon & Interventional Cardiologist) Review Randomized if suitable for either CABG or PCI or Enrolled in nested registry if not equally suitable CABG Reg. n=649* CABG RCT n=897 PCI RCT n=903 PCI Registry n=198 Enrolled CABG n=644** From SYNTAX_CSR_randomized_Unblinded_2008Oct10.doc Exhibit 5 SYNTAX 5-Year Report_Randomized_15JUN12.doc Exhibit 4 (evaluable for 5-year MACCE) SYNTAX 5-Year Report_Registry_22JUN12.doc Exhibits 4 and 8 CABG 849 (94.6%) PCI 891 (98.7%) PCI n=192** Primary Endpoint 1 Year Follow-up CABG 610 (94.7%) CABG 805 (89.7%) Completed Study 5 Year Follow-up PCI 871 (96.5%) PCI 188 (97.9%) *N=649 followed for 5 years, N=1077 enrolled, **CABG N=644, PCI N=192 treated per protocol. PCI performed with TAXUS Express

Patient Characteristics CABG RCT N=897 PCI RCT N=903 P value CABG Registry N=644 PCI Registry N=192 Age* (y) 65.0±9.8 65.2±9.7 0.55 65.7±9.4 71.2±10.4 Male, % 78.9 76.4 0.20 80.7 70.3 Diabetes*†, % 24.6 25.6 0.64 26.4 30.2 Additive euroSCORE* 3.8±2.7 3.8±2.6 0.78 3.9±2.7 5.8±3.1 Total Parsonnet score* 8.4±6.8 8.5±7.0 0.76 9.0±7.1 14.4±9.5 Total SYNTAX Score 29.1±11.4 28.4±11.5 0.19 37.8±13.3 31.6±12.3 Mean # of lesions 4.4±1.8 4.3±1.8 0.44 4.6±1.7 4.5±1.8 3VD only, % 66.3 65.4 0.70 59.7 66.7 Left main, any, % 33.7 34.6 40.3 33.3 Total occlusion, % 22.2 24.2 0.33 56.4 36.5 Complete revasc, % 63.2 56.7 0.005 74.7 From SYNTAX_CSR_randomized_Unblinded_2008Oct10.doc Exhibit 6,7,9 SYNTAX CSR Registry Unblinded_2008Oct10.doc Exhibits 5, 6, 8, 24, 25, 27 Values are mean±SD or %. Core laboratory reported unless *Site-reported †Medically treated 4

All-Cause Death to 5 Years TAXUS (N=903) CABG (N=897) Before 1 year* 3.5% vs 4.4% P=0.37 1-2 years* 1.5% vs 1.9% P=0.53 2-3 years* 1.9% vs 2.6% P=0.32 3-4 years* 2.2% vs 3.2% P=0.22 4-5 years* 3.1% vs 2.3% P=0.34 25 50 P=0.10 Cumulative Event Rate (%) 1 yr data From SYNTAX_CSR_randomized_Unblinded_2008Oct10.doc exhibit 1 2-Year_Randomized_20090917.doc Exhibit 2 (binary interval rate) SYNTAX 3-Year Report_Randomized_12JUL10.doc Exhibit 2 (binary interval rate) SYNTAX 4-Year Report_Randomized_15JUN11.doc exhibits 1 (KM rate on right sidea) and exhibit 2 (binary interval rate in white box) 13.9% 11.4% 12 60 24 36 48 Months Since Allocation Cumulative KM Event Rate ± 1.5 SE; log-rank P value;*Binary rates ITT population 5

Cardiac Death to 5 Years TAXUS (N=903) CABG (N=897) 25 50 P=0.003 Before 1 year* 2.1% vs 3.7% P=0.0503 1-2 years* 0.6% vs 0.8% P=0.62 2-3 years* 0.9% vs 1.6% P=0.22 3-4 years* 0.8% vs 1.6% P=0.13 4-5 years* 1.1% vs 1.4% P=0.56 25 50 P=0.003 Cumulative Event Rate (%) 1 yr data From SYNTAX_CSR_randomized_Unblinded_2008Oct10.doc exhibit 1 2-Year_Randomized_20090917.doc Exhibit 2 (binary interval rate) SYNTAX 3-Year Report_Randomized_12JUL10.doc Exhibit 2 (binary interval rate) SYNTAX 4-Year Report_Randomized_15JUN11.doc exhibits 1 (KM rate on right sidea) and exhibit 2 (binary interval rate in white box) 9.0% 5.3% 12 60 24 36 48 Months Since Allocation Cumulative KM Event Rate ± 1.5 SE; log-rank P value;*Binary rates ITT population 6

Myocardial Infarction to 5 Years TAXUS (N=903) CABG (N=897) Before 1 year* 3.3% vs 4.8% P=0.11 1-2 years* 0.1% vs 1.2% P=0.008 2-3 years* 0.3% vs 1.2% P=0.03 3-4 years* 0.3% vs 1.5% P=0.01 4-5 years* 0% vs 1.2% P=0.004 25 50 P<0.001 Cumulative Event Rate (%) 1 yr data From SYNTAX_CSR_randomized_Unblinded_2008Oct10.doc exhibit 1 2-Year_Randomized_20090917.doc Exhibit 2 (binary interval rate) SYNTAX 3-Year Report_Randomized_12JUL10.doc Exhibit 2 (binary interval rate) SYNTAX 4-Year Report_Randomized_15JUN11.doc exhibits 1 (KM rate on right sidea) and exhibit 2 (binary interval rate in white box) 9.7% 3.8% 12 60 24 36 48 Months Since Allocation Cumulative KM Event Rate ± 1.5 SE; log-rank P value;*Binary rates ITT population 7

CVA to 5 Years TAXUS (N=903) CABG (N=897) 25 50 P=0.09 Before 1 year* 2.2% vs 0.6% P=0.003 1-2 years* 0.6% vs 0.7% P=0.82 2-3 years* 0.5% vs 0.6% P=1.00 3-4 years* 0.4% vs 0.2% P=0.68 3-4 years* 0% vs 0.1% P=1.00 25 50 P=0.09 Cumulative Event Rate (%) 1 yr data From SYNTAX_CSR_randomized_Unblinded_2008Oct10.doc exhibit 1 2-Year_Randomized_20090917.doc Exhibit 2 (binary interval rate) SYNTAX 3-Year Report_Randomized_12JUL10.doc Exhibit 2 (binary interval rate) SYNTAX 4-Year Report_Randomized_15JUN11.doc exhibits 1 (KM rate on right sidea) and exhibit 2 (binary interval rate in white box) 3.7% 2.4% 12 60 24 36 48 Months Since Allocation Cumulative KM Event Rate ± 1.5 SE; log-rank P value;*Binary rates ITT population 8

All-Cause Death/CVA/MI to 5 Years TAXUS (N=903) CABG (N=897) Before 1 year* 7.7% vs 7.6% P=0.98 1-2 years* 2.2% vs 3.5% P=0.11 2-3 years* 2.5% vs 3.8% P=0.14 3-4 years* 2.7% vs 4.6% P=0.051 4-5 years* 3.1% vs 3.1% P=0.98 25 50 P=0.03 Cumulative Event Rate (%) 20.8% 1 yr data From SYNTAX_CSR_randomized_Unblinded_2008Oct10.doc exhibit 1 2-Year_Randomized_20090917.doc Exhibit 2 (binary interval rate) SYNTAX 3-Year Report_Randomized_12JUL10.doc Exhibit 2 (binary interval rate) SYNTAX 4-Year Report_Randomized_15JUN11.doc exhibits 1 (KM rate on right sidea) and exhibit 2 (binary interval rate in white box) 16.7% 12 60 24 36 48 Months Since Allocation Cumulative KM Event Rate ± 1.5 SE; log-rank P value;*Binary rates ITT population 9

Repeat Revascularization to 5 Years TAXUS (N=903) CABG (N=897) Before 1 year* 5.9% vs 13.5% P<0.001 1-2 years* 3.7% vs 5.6% P=0.06 2-3 years* 2.5% vs 3.4% P=0.33 3-4 years* 1.6% vs 4.2% P=0.002 4-5 years* 1.9% vs 4.3% P=0.008 25 50 P<0.001 25.9% Cumulative Event Rate (%) 1 yr data From SYNTAX_CSR_randomized_Unblinded_2008Oct10.doc exhibit 1 2-Year_Randomized_20090917.doc Exhibit 2 (binary interval rate) SYNTAX 3-Year Report_Randomized_12JUL10.doc Exhibit 2 (binary interval rate) SYNTAX 4-Year Report_Randomized_15JUN11.doc exhibits 1 (KM rate on right sidea) and exhibit 2 (binary interval rate in white box) 13.7% 12 60 24 36 48 Months Since Allocation Cumulative KM Event Rate ± 1.5 SE; log-rank P value;*Binary rates ITT population 10

MACCE to 5 Years TAXUS (N=903) CABG (N=897) 25 50 P<0.001 37.3% Before 1 year* 12.4% vs 17.8% P=0.002 1-2 years* 5.7% vs 8.3% P=0.03 2-3 years* 4.8% vs 6.7% P=0.10 3-4 years* 4.2% vs 7.9% P=0.002 4-5 years* 5.0% vs 6.3% P=0.27 25 50 P<0.001 37.3% Cumulative Event Rate (%) 26.9% 1 yr data From SYNTAX_CSR_randomized_Unblinded_2008Oct10.doc exhibit 1 2-Year_Randomized_20090917.doc Exhibit 2 (binary interval rate) SYNTAX 3-Year Report_Randomized_12JUL10.doc Exhibit 2 (binary interval rate) SYNTAX 4-Year Report_Randomized_15JUN11.doc exhibits 1 (KM rate on right sidea) and exhibit 2 (binary interval rate in white box) 12 60 24 36 48 Months Since Allocation Cumulative KM Event Rate ± 1.5 SE; log-rank P value;*Binary rates ITT population 11

Per Protocol Graft Occlusion or Stent Thrombosis to 5 Years (Per Patient Binary Rates) PCI CABG Patients (%) (3/870) (3/868) (12/854) (2/812) (6/790) (3/764) (3/729) (32/581) SYNTAX 5-Year Report_Randomized_22JUN12.doc Exhibit 9 (2/896) (18/893) (8/874) (5/850) (4/830) (7/803) (5/768) (47/708) Acute ≤1d Subacute 2-30d Late 31-365d Very Late Total 5 year 366- 730d 731- 1095d 1096- 1460d 1461- 1825d Days Postprocedure Per protocol GO and ST: clinical presentation of ACS with angiographically confirmed occlusion within/adjacent to a previously successfully treated lesion/graft during follow-up and/or Q-wave MI in the treated vessel territory within 30 d of the index procedure. Numbers are per patient, 1PCI patient had an ST 1d and 6d post-procedure; therefore, counted in the ≤1d and 2-30d intervals but only once in the total. 12

MACCE to 5 Years by SYNTAX Score Tercile Low Scores (0-22) TAXUS (N=299) CABG (N=275) CABG PCI P value Death 10.1% 8.9% 0.64 CVA 4.0% 1.8% 0.11 MI 4.2% 7.8% Death, CVA or MI 14.9% 16.1% 0.81 Revasc. 16.9% 23.0% 0.06 Overall 50 32.1% P=0.43 Cumulative Event Rate (%) 25 28.6% SYNTAX 5-Year Report_Randomized_15JUN12.doc exhibit 53 12 24 36 48 60 Months Since Allocation Cumulative KM Event Rate ± 1.5 SE; log-rank P value Core lab-reported Data; ITT population

MACCE to 5 Years by SYNTAX Score Tercile Intermediate Scores (23-32) TAXUS (N=310) CABG (N=300) CABG PCI P value Death 12.7% 13.8% 0.68 CVA 3.6% 2.0% 0.25 MI 11.2% <0.001 Death, CVA or MI 18.0% 20.7% 0.42 Revasc. 24.1% Overall 50 36.0% P=0.008 Cumulative Event Rate (%) 25 SYNTAX 5-Year Report_Randomized_15JUN12.doc exhibit 55 25.8% 12 24 36 48 60 Months Since Allocation Cumulative KM Event Rate ± 1.5 SE; log-rank P value Core lab-reported Data; ITT population

MACCE to 5 Years by SYNTAX Score Tercile High Scores (33) TAXUS (N=290) CABG (N=315) CABG PCI P value Death 11.4% 19.2% 0.005 CVA 3.7% 3.5% 0.80 MI 3.9% 10.1% 0.004 Death, CVA or MI 17.1% 26.1% 0.007 Revasc. 12.1% 30.9% <0.001 Overall 50 P<0.001 44.0% Cumulative Event Rate (%) 25 26.8% SYNTAX 5-Year Report_Randomized_15JUN12.doc exhibit 57 12 24 36 48 60 Months Since Allocation Cumulative KM Event Rate ± 1.5 SE; log-rank P value Core lab-reported Data; ITT population

The 5-year Outcomes of the SYNTAX Trial CABG Registry and PCI Registry

MACCE to 5 Years SYNTAX CABG Registry CABG Registry (n=644) SYNTAX Score: 37.8±13.3 Additive EuroSCORE: 3.9±2.7 Complete revascularization: 74.7% Patients (%) 23.2 SYNTAX 5-Year Report_Registry_15JUN12.doc Exhibit 5 for graph and SYNTAX CSR Registry_Unblinded_2008Oct10.doc Exhibits 24, 25, 27 for text box All Death Cardiac Death MI CVA Revasc. MACCE 17

MACCE to 5 Years SYNTAX PCI Registry PCI Registry (n=192) SYNTAX Score: 31.6 ± 12.3 Additive EuroSCORE: 5.8 ± 3.1 Complete revascularization: 36.5% 49.2 Patients (%) SYNTAX 5-Year Report_Registry_15JUN12.doc exhibit 1 for graph and SYNTAX CSR Registry_Unblinded_2008Oct10.doc Exhibits 5,6, 8 for text box All Death Cardiac Death MI CVA Revasc. MACCE 18

MACCE to 5 Years Interpreting Results Based on SYNTAX Score PCI only 7% CABG only PCI or CABG 71% 22% Get totals for # of patients from: SYNTAX 5-Year Report_Registry_22JUN12.doc Exhibits 1 and 5 for PCI and CABG Registries SYNTAX 5-Year Report_Randomized_15JUN12.doc exhibits 53, 55, and 57 for SYNTAX Score groups Add number of patients in registries and SYNTAX Score groups to get total # of patients in trial Calculate percentages by hand as follows: For CABG only: Number of patients in (CABG Registry)+(23 to 32 group)+(33+ group) divided by total number of patients in trial (numerator should also be the # of patients in blue wedges in pie chart) For PCI or CABG: Number of patients in (0 to 22 group) divided by total number of patients in trial PCI Only: Number of patients in (PCI Registry) divided by total number of patients in trial. Five-year results of the SYNTAX trial suggest that 71% of all patients are still best treated with CABG; however, for the remaining patients PCI is an alternative to surgery

Thank you to the SYNTAX Steering Committee and Investigators Summary & Conclusions The final 5-year results of the SYNTAX trial demonstrate that surgery remains the gold standard for patients with complex multivessel disease In patients with less complex disease, PCI is an acceptable alternative treatment Treatment decisions for an individual patient should continue to be made in consultation between the patient and the Heart Team, while considering the risks and benefits of the respective treatment options Thank you to the SYNTAX Steering Committee and Investigators